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OBJECTIVES: Discovering airway gene expression alterations associated with radiological bronchiectasis may improve the understanding of the pathobiology of early-stage bronchiectasis. METHODS: Presence of radiological bronchiectasis in 173 individuals without a clinical diagnosis of bronchiectasis was evaluated. Bronchial brushings from these individuals were transcriptomically profiled and analysed. Single-cell deconvolution was performed to estimate changes in cellular landscape that may be associated with early disease progression. RESULTS: 20 participants have widespread radiological bronchiectasis (three or more lobes). Transcriptomic analysis reflects biological processes associated with bronchiectasis including decreased expression of genes involved in cell adhesion and increased expression of genes involved in inflammatory pathways (655 genes, false discovery rate <0.1, log2 fold-change >0.25). Deconvolution analysis suggests that radiological bronchiectasis is associated with an increased proportion of ciliated and deuterosomal cells, and a decreased proportion of basal cells. Gene expression patterns separated participants into three clusters: normal, intermediate and bronchiectatic. The bronchiectatic cluster was enriched by participants with more lobes of radiological bronchiectasis (p<0.0001), more symptoms (p=0.002), higher SERPINA1 mutation rates (p=0.03) and higher computed tomography derived bronchiectasis scores (p<0.0001). CONCLUSIONS: Genes involved in cell adhesion, Wnt signalling, ciliogenesis and interferon-γ pathways had altered expression in the bronchus of participants with widespread radiological bronchiectasis, possibly associated with decreased basal and increased ciliated cells. This gene expression pattern is not only highly enriched among individuals with radiological bronchiectasis, but also associated with airway-related symptoms in those without discernible radiological bronchiectasis, suggesting that it reflects a bronchiectasis-associated, but non-bronchiectasis-specific lung pathophysiological process.
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Bronquiectasia , Humanos , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/genética , Bronquios/diagnóstico por imagen , Radiografía , Tomografía Computarizada por Rayos X/métodos , Expresión GénicaRESUMEN
Reasonable treatment of large amounts of sludge excavated from landfills has gained increasing attention due to the diminishing availability of landfill space in China. In this study, five landfill sludge (LS) treatment technologies using life cycle assessment (LCA) and life cycle cost (LCC) were investigated, i.e., co-incineration in coal-fired power plants (CFPP) and waste incineration power plant (WIPP), co-processing in cement kiln, bricks production, and sintering ceramsite. The LCA results demonstrate that sintering ceramsite outperforms other technologies and LCC results indicate sintering ceramsite also provides the highest economic benefit ($869.94). To further enhance environmental and economic performances of the LS treatment, the substitution of coal with natural gas and biomass can reduce Energy Conservation and Emission Reduction (ECER) index by 74% and 98%, respectively. This substitution can increase economic returns by 24% and 26%, respectively. Furthermore, national-level economic benefit and carbon emission reduction potential of different LS treatment technology alternative scenarios were assessed. Results display that a combination of 50% CFPP, 25% bricks, and 25% ceramsite (biomass) offers the highest economic gain, which is 3.02 times that of 50% CFPP and 50% cement (original case). Conversely, the replacement of 25% brick with 25% cement in the above combination result in the lowest carbon reduction, which is 9.35 times that of the original case.
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Aguas del Alcantarillado , Instalaciones de Eliminación de Residuos , China , Incineración , Carbón MineralRESUMEN
Paper mill sludge (PMS) is featured with a high content of cellulose and hemicellulose, and using its characteristics to make paperboard can achieve a high-value utilization of PMS, which has attracted growing interest. In this study, currently prevalent landfill, incineration technologies (generating heat and electricity by incineration), and three paperboard technologies (medium density fiberboard, pulp board, and corrugated paper) were evaluated and compared via life cycle assessment (LCA) and life cycle costing (LCC) methods. LCA results show that the PMS-to-pulp board outperforms others with an energy conservation and emission reduction (ECER) value of - 2.86 × 10-8, while the landfill exhibits the highest overall environmental impact with an ECER value of 4.80 × 10-9. LCC results reveal that the PMS-to-pulp board delivers the highest economic profit with $257.357, while the landfill is the lowest with $ - 35.63. The PMS paperboard technologies are more economically friendly than the incineration technologies due to additional electricity/steam consumption during the PMS pre-drying process in incineration. In addition, different scenarios were set up to explore national GHG emission reduction potential by increasing paperboard technologies application rate and reducing the proportion of landfill and incineration. The scenario analysis suggests that replacing 90% of landfill and incineration ratio with PMS paperboard technologies could tremendously improve the overall emission reduction performance with - 9.08 × 1010 kg CO2 eq. This result indicates that the PMS treatment technology transformation has a significant favorable impact on the achievement of the "carbon neutrality" target.
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Incineración , Papel , Aguas del Alcantarillado , ChinaRESUMEN
As a new technology for accurate utilization of sludge resources, sludge inorganic-organic matter separation (IOMS) has attracted wide attention. This study examined the impact of this pretreatment on environmental and economic performance of sludge composting and incineration using life cycle assessment (LCA) and whole life costing (WLC). LCA results indicated that IOMS pretreatment reduced the energy conservation and emission reduction (ECER) values of composting and incineration by 56 % and 76 %, respectively. Meanwhile, WLC exhibited that IOMS pretreatment could cut the break-even year of incineration from 11 years to 4 years. The combination of organic sludge incineration/composting with inorganic sludge sintering ceramsite reveals excellent environmental and economic performance. The application optimization hypothesis analysis of these two routes in various provinces of China indicates that Jiangsu has the greatest development potential and should become a major promotion region.
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Aguas del Alcantarillado , Compostaje/métodos , Incineración , Ambiente , ChinaRESUMEN
Microscopic vascular invasion (VI) is predictive of recurrence and benefit from lobectomy in stage I lung adenocarcinoma (LUAD) but is difficult to assess in resection specimens and cannot be accurately predicted prior to surgery. Thus, new biomarkers are needed to identify this aggressive subset of stage I LUAD tumors. To assess molecular and microenvironment features associated with angioinvasive LUAD we profiled 162 resected stage I tumors with and without VI by RNA-seq and explored spatial patterns of gene expression in a subset of 15 samples by high-resolution spatial transcriptomics (stRNA-seq). Despite the small size of invaded blood vessels, we identified a gene expression signature of VI from the bulk RNA-seq discovery cohort (n=103) and found that it was associated with VI foci, desmoplastic stroma, and high-grade patterns in our stRNA-seq data. We observed a stronger association with high-grade patterns from VI+ compared with VI- tumors. Using the discovery cohort, we developed a transcriptomic predictor of VI, that in an independent validation cohort (n=60) was associated with VI (AUROC=0.86; p=5.42×10-6) and predictive of recurrence-free survival (HR=1.98; p=0.024), even in VI- LUAD (HR=2.76; p=0.003). To determine our VI predictor's robustness to intra-tumor heterogeneity we used RNA-seq data from multi-region sampling of stage I LUAD cases in TRACERx, where the predictor scores showed high correlation (R=0.87, p<2.2×10-16) between two randomly sampled regions of the same tumor. Our study suggests that VI-associated gene expression changes are detectable beyond the site of intravasation and can be used to predict the presence of VI. This may enable the prediction of angioinvasive LUAD from biopsy specimens, allowing for more tailored medical and surgical management of stage I LUAD.
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Harmless disposal and reutilization of electroplating sludge (ES) attract growing interests due to the high content of heavy metals, which requires economical-affordable and environmentally friendly processing technologies. Main reutilization alternatives in China, i.e., acid leaching, bioleaching, smelting, ironmaking blast furnace co-processing (IBFC), and cement kiln co-processing (CKC), were evaluated and compared via life cycle assessment (LCA) and life cycle costing (LCC) methods. In addition, the heavy metal recovery potential of these scenarios was also evaluated to focus on the sustainable use of metal resources. LCA results show that acid leaching outperforms other scenarios due to the environmental benefits originating from recovering heavy metals, while smelting exhibits the worst due to high energy consumption. The environmental contribution analysis reveals that the product nickel sulfate has a significant positive impact on acid leaching and bioleaching scenarios, and energy consumption is the key factor for smelting, IBFC, and CKC. LCC results show that bioleaching outperforms others, while CKC performs the worst because only inorganic materials are utilized. Bioleaching has the lowest externality cost while CKC has the highest. The heavy metal recovery assessment indicates that bioleaching exhibits the greatest potential with recovery rates of 99%, 99%, 93%, 96%, and 95% for Cu, Cr, Ni, Zn, and Fe, respectively. In contrast, the target heavy metal recovery rate for both acid leaching and smelting is 93%. Acid leaching and bioleaching scenarios are more advantageous from a comprehensive comparison.
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Metales Pesados , Aguas del Alcantarillado , Galvanoplastia , Metales Pesados/análisis , ChinaRESUMEN
Food waste (FW) treatment has attracted increasing attention since waste classification occurred in China. Analyzing the environmental and economic impacts of different FW treatment technologies is required. In this study, four FW treatments, i.e., anaerobic digestion, black soldier fly (BSF) bioconversion, composting, and landfill, were evaluated using life cycle assessment (LCA) and life cycle cost (LCC). LCA results show that anaerobic digestion outperforms the other technologies, while LCC results indicate anaerobic digestion has the lowest economic benefits ($5.16) and landfill has the highest ($14.22). Bioconversion has the highest product revenue ($37.98). FW anaerobic digestion followed by treating digestate and waste crude oil was employed to investigate the environmental differences between waste classification and mixed incineration. Digestate gasification and conversion of waste crude oil to biodiesel are found to be environmentally friendly, and waste classification outperforms mixed incineration. Furthermore, we explored national-level environmental emission reduction with anaerobic digestion as the dominant technology via increasing resource utilization rate and applying household FW disposers. Results display that a 60% resource utilization rate decreases the overall environmental impact by 36.68% compared with current situation, and treating household FW separately at the source can further lead to emission reduction. This study provides a reference for selecting FW technologies for countries worldwide from environmental and economic perspectives, as well as a direction of resource utilization for how to reduce environmental emissions from treating the total FW produced by all humanity.
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Eliminación de Residuos , Administración de Residuos , Animales , Alimentos , China , Estadios del Ciclo de VidaRESUMEN
The reduction of greenhouse gas (GHG) emissions from solid waste incinerator fly ash (IFA) management attracts growing interests since China's zero-waste plan and carbon peak/neutral goals. Herein, provincial GHG emissions from four demonstrated IFA reutilization technologies in China were estimated after analyzing IFA spatial-temporal distribution. Results indicate that technologies transition (landfilling-to-reutilization) could reduce GHG except for glassy slag production. IFA to cement option could potentially realize negative GHG emissions. Spatial GHG variation drivers in IFA management were recognized as provincial-different IFA composition and power emission factors. IFA management options were recommended provincially after weighting local development goals related to GHG reduction and economic benefits. Baseline scenario analysis shows that China's IFA industry would reach carbon peak in 2025 (5.02 Mt). 2030's GHG reduction potential (6.12 Mt) is equivalent to that of absorbed CO2 by 340 million trees annually. Overall, this research could contribute to illustrating future market layout complying with carbon peaking.
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The surge of medical waste (MW) generated during the COVID-19 pandemic has exceeded the disposal capacity of existing facilities. The timely, safe, and efficient emergency disposal of MW is critical to prevent the epidemic spread. Therefore, this review presents the current status of MW generation and disposal in China and analyzes the characteristics and applicability of emergency disposal technologies. The results show that movable disposal facilities can dispose of infectious MW on site, even though most of their disposal capacity is at a low level (<5 t/day). Co-disposal facilities need to be reformed completely for emergency MW disposal, in which separate feeding systems should be taken seriously. Specifically, municipal solid waste (MSW) incineration facilities have great potential to improve emergency MW disposal capacities. For hazardous waste incineration facilities, compatibility of the wastes must be matched to the composition and calorific value of the waste. As for cement kiln, MW can only be used as an alternative fuel instead of a raw material for cement. Based on the environmental risk and technical adaptability, the six emergency MW disposal technologies are recommended to be prioritized as follows: movable microwave sterilization, movable steam sterilization, movable incineration, co-incineration with hazardous waste, co-incineration with MSW and co-disposal in cement kilns. Infectious MW, especially COVID-19 MW, should be prioritized for disposal by centralized and movable disposal facilities, while non-infectious MW can be disposed of using co-disposal facilities. All stakeholders should strengthen the delicacy management of the end-of-life stage of MW, including collection, classification, packaging identification, transportation, and disposal. Currently, it is necessary for centralized disposal enterprises to follow the emergency disposal operation flowchart. From a long-term strategic perspective, making full use of regional movable and co-disposal facilities in the megacities can effectively enhance the emergency MW disposal capacity.
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COVID-19 , Eliminación de Residuos Sanitarios , Residuos Sanitarios , Eliminación de Residuos , Administración de Residuos , China/epidemiología , Humanos , Incineración , Pandemias , SARS-CoV-2 , Residuos Sólidos/análisis , Instalaciones de Eliminación de ResiduosRESUMEN
The dispersed sources and inconvenient transportation of rural domestic waste (RDW) lead to difficult centralized treatment. Gasification is suitable for decentralized waste treatment, which can effectively avoid RDW long-distance transportation and reduce dioxin emissions compared with small-scale incineration. Hence, economically-affordable and environmentally-friendly RDW treatment models with different gasification scales are required, and village, town and county models were compared via life cycle assessment (LCA) and life cycle cost (LCC) methods in this study. Furthermore, scenario analysis investigated waste sorting based on two food waste (FW) treatment technologies, different FW separate collection efficiency, and electricity recovery to explore the environmental and economic improvement potentials of three models. LCA results show that electricity consumption and direct emissions are significant contributors to environmental impacts, and the county model outperforms village and town models. Moreover, transportation accounts for 6% of the overall environmental impact in the county model. Scenario analysis reveals that waste sorting and electricity recovery can reduce the overall environmental impact by 29% to 146% for three models. LCC results demonstrate that the town model delivers the lowest economic cost, while the village model is the highest. In scenario analysis, resource utilization of FW and electricity recovery of other waste exhibit promising economic benefits. The findings provide comprehensive references for sustainable RDW treatment.
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Plant cell expands via a tip growth or diffuse growth mode. In plants, RabA is the largest group of Rab GTPases that regulate vesicle trafficking. The functions of RabA protein in modulating polarized expansion in tip growth cells have been demonstrated. However, whether and how RabA protein functions in diffuse growth plant cells have never been explored. Here, we addressed this question by examining the role of GhRabA4c in cotton fibers. GhRabA4c was preferentially expressed in elongating fibers with its protein localized to endoplasmic reticulum and Golgi apparatus. Over- and down-expression of GhRabA4c in cotton lead to longer and shorter fibers, respectively. GhRabA4c interacted with GhACT4 to promote the assembly of actin filament to facilitate vesicle transport for cell wall synthesis. Consistently, GhRabA4c-overexpressed fibers exhibited increased content of wall components and the transcript levels of the genes responsible for the synthesis of cell wall materials. We further identified two MYB proteins that directly regulate the transcription of GhRabA4c Collectively, our data showed that GhRabA4c promotes diffused cell expansion by supporting vesicle trafficking and cell wall synthesis.
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Citoesqueleto de Actina , Fibra de Algodón , Citoesqueleto de Actina/metabolismo , Transporte Biológico , Aparato de Golgi/metabolismo , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismoRESUMEN
The chemopreventive effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-lipoxygenase inhibitor, has additive activity with NSAIDs against tobacco carcinogenesis in preclinical models. We hypothesized that cyclooxygenase plus 5-lipoxygenase inhibition would be more effective than a placebo in modulating the nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low-dose aspirin plus zileuton vs. double placebo in current smokers to compare the modulating effects on nasal gene expression and arachidonic acid metabolism. In total, 63 participants took aspirin 81 mg daily plus zileuton (Zyflo CR) 600 mg BID or the placebo for 12 weeks. Nasal brushes from the baseline, end-of-intervention, and one-week post intervention were profiled via microarray. Aspirin plus zilueton had minimal effects on the modulation of the nasal or bronchial gene expression signatures of smoking, lung cancer, and COPD but favorably modulated a bronchial gene expression signature of squamous dysplasia. Aspirin plus zileuton suppressed urinary leukotriene but not prostaglandin E2, suggesting shunting through the cyclooxygenase pathway when combined with 5-lipoxygenase inhibition. Continued investigation of leukotriene inhibitors is needed to confirm these findings, understand the long-term effects on the airway epithelium, and identify the safest, optimally dosed agents.
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SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48+ secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.
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COVID-19 , Neoplasias Pulmonares , Humanos , SARS-CoV-2/genética , Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Detección Precoz del Cáncer , Peptidil-Dipeptidasa A/metabolismo , Neoplasias Pulmonares/metabolismo , Bronquios/metabolismo , Fumar/efectos adversos , Fumar/genéticaRESUMEN
Medical waste (MW) has exploded since the COVID-19 pandemic and aroused great concern to MW disposal. Meanwhile, the energy recovery for MW disposal is necessary due to high heat value of MW. Harmless disposal of MW with economically and environmentally sustainable technologies along with higher energy recovery is urgently required, and their energy recovery efficiencies and environmental impacts reduction due to energy recovery are key issues. In this study, five MW disposal technologies, i.e. rotary kiln incineration, pyrolysis incineration, plasma melting, steam sterilization and microwave sterilization, were evaluated and compared via energy recovery analysis (ERA), life cycle assessment (LCA), and life cycle costing (LCC) methods. Furthermore, three MW incineration technologies with further energy recovery and two sterilization followed by co-incineration technologies were analyzed to explore their improvement potential of energy recovery and environment benefits via scenario analysis. ERA results reveal that the energy recovery efficiencies of "steam and microwave sterilization + incineration" are the highest (≥83.4%), while that of the plasma melting is the lowest (19.2%). LCA results show that "microwave sterilization + landfill" outperforms others while the plasma melting exhibits the worst, electricity is the most significant contributor to the environmental impacts of five technologies. Scenario analysis shows that the overall environmental impact of all technologies reduced by at least 45% after further heat utilization. LCC results demonstrate that pyrolysis incineration delivers the lowest economic cost, while plasma melting is the highest. Co-incineration of sterilized MW and municipal solid waste could be recommended.
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COVID-19 , Eliminación de Residuos Sanitarios , Eliminación de Residuos , China , Humanos , Pandemias , SARS-CoV-2RESUMEN
The COVID-19 pandemic attracts concerns globally and leads to an exponential increase in medical waste generation, and disposal of medical waste is an urgent need for preventing the epidemic spread. Emergency disposal scenarios of medical waste generated during the COVID-19 pandemic require a systematic assessment to quantify their potential environmental impacts. The environmental impacts and key factors of three movable disposal scenarios (i.e. incineration disposal vehicle, movable steam and microwave sterilization equipment both followed by co-incineration with municipal solid waste) were quantified via life cycle assessment approach. Furthermore, the environmental impacts of three movable disposal and two co-incineration scenarios were compared via life cycle assessment by expanding system boundaries. The results show that co-incineration with municipal solid waste has the lowest environmental impacts due to environmental benefits produced by power generation, while co-incineration with hazardous waste is the highest due to the high energy consumption. Energy consumption (i.e. kerosene, electricity and diesel) are the key factors for three movable disposal scenarios. For movable steam and microwave sterilization equipment followed by co-incineration with municipal solid waste, power generation from incinerating disinfected medical waste has significant beneficial environmental impacts due to avoided impacts of electricity consumption. The recommendations for improvement of the emergency disposal and management of medical waste during the COVID-19 pandemic globally and other serious epidemic in the future are provided.
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COVID-19 , Residuos Sanitarios , Eliminación de Residuos , Administración de Residuos , Animales , China , Humanos , Incineración , Estadios del Ciclo de Vida , Pandemias , SARS-CoV-2 , Residuos Sólidos/análisis , Instalaciones de Eliminación de ResiduosRESUMEN
OBJECTIVE: The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological, and molecular features. METHODS: Endobronchial biopsies (n=295) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via autofluorescence bronchoscopy and CT, were profiled by RNA-seq. We applied the TCR Repertoire Utilities for Solid Tissue/Tumor tool to the RNA-seq data to identify TCR CDR3 sequences across all samples. In the biopsies, we measured the correlation of TCR diversity with previously derived immune-associated PML transcriptional signatures and PML outcome. We also quantified the spatial and temporal distribution of shared and clonally expanded TCRs. Using the biopsies and brushes, the ratio of private (ie, found in one patient only) and public (ie, found in two or more patients) TCRs was quantified, and the CDR3 sequences were compared with those found in curated databases with known antigen specificities. RESULTS: We detected 39,303 unique TCR sequences across all samples. In PML biopsies, TCR diversity was negatively associated with a transcriptional signature of T cell mediated immune activation (p=4e-4) associated with PML outcome. Additionally, in lesions of the proliferative molecular subtype, TCR diversity was decreased in regressive versus progressive/persistent PMLs (p=0.045). Within each patient, TCRs were more likely to be shared between biopsies sampled at the same timepoint than biopsies sampled at the same anatomic location at different times. Clonally expanded TCRs, within a biopsied lesion, were more likely to be expanded at future time points than non-expanded clones. The majority of TCR sequences were found in a single sample, with only 3396 (8.6%) found in more than one sample and 1057 (2.7%) found in two or more patients (ie, public); however, when compared with a public database of CDR3 sequences, 4543 (11.6%) of TCRs were identified as public. TCRs with known antigen specificities were enriched among public TCRs (p<0.001). CONCLUSIONS: Decreased TCR diversity may reflect nascent immune responses that contribute to PML elimination. Further studies are needed to explore the potential for immunoprevention of PMLs.
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Neoplasias Pulmonares/genética , Neoplasias de Células Escamosas/genética , Linfocitos T/inmunología , Progresión de la Enfermedad , Femenino , Humanos , MasculinoRESUMEN
INTRODUCTION: Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent BAC-like adenocarcinoma. METHODS: Since the frequency of indolent cancers has not been compared between CTLS and routinely detected cohorts, we compare pathology and RNA expression of 86 NCCN high-risk CTLS subjects to 83 high-risk (HR-R) and 51 low-risk (LR-R) routinely detected patients. Indolent adenocarcinoma was defined as previously described for low malignant potential (LMP) adenocarcinoma along with AIS/MIA. Exome RNA sequencing was performed on a subset of high-risk (CTLS and HR-R) FFPE tumor samples. RESULTS: Indolent adenocarcinoma (AIS, MIA, and LMP) showed 100% disease-specific survival (DSS) with similar frequency in CTLS (18%) and HR-R (20%) which were comparatively lower than LR-R (33%). Despite this observation, CTLS exhibited intermediate DSS between HR-R and LR-R (5-year DSS: 88% CTLS, 82% HR-R, & 95% LR-R, p = 0.047), possibly reflecting a 0.4 cm smaller median tumor size and lower frequency of tumor necrosis compared to HR-R. WGCNA gene modules derived from TCGA lung adenocarcinoma correlated with aggressive histologic patterns, mitotic activity, and tumor invasive features, but no significant differential expression between CTLS and HR-R was observed. CONCLUSION: CTLS subjects are at no greater risk of overdiagnosis from indolent adenocarcinoma (AIS, MIA, and LMP) than risk-matched patients whose cancers are discovered in routine clinical practice. Improved outcomes likely reflect detection and treatment at smaller size.
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Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/diagnóstico , Expresión Génica/genética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/patología , Anciano , Estudios de Cohortes , Detección Precoz del Cáncer , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
Background : SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments has not been fully characterized using matched samples from large cohorts. Results : Gene expression data from 793 nasal and 1,673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking was the only clinical factor significantly and reproducibly associated with VE gene expression. ACE2 and TMPRSS2 expression were higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48 + secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the RNA-seq confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. Conclusions : The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose these genes are not predominantly expressed in cell populations modulated by smoking. Smoking-induced VE gene expression changes in the nose likely has minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.
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BACKGROUND: Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using CT imaging has identified several clinically relevant subgroups of smoking related lung disease, but these investigations have generally lacked organ specific molecular correlates. RESEARCH QUESTION: Can CT imaging be used to identify clinical phenotypes of smoking related lung disease that have specific bronchial epithelial gene expression patterns to better understand disease pathogenesis? STUDY DESIGN AND METHODS: Using K-means clustering, we clustered participants from the COPDGene study (n = 5,273) based on CT imaging characteristics and then evaluated their clinical phenotypes. These clusters were replicated in the Detection of Early Lung Cancer Among Military Personnel (DECAMP) cohort (n = 360), and were further characterized using bronchial epithelial gene expression. RESULTS: Three clusters (preserved, interstitial predominant and emphysema predominant) were identified. Compared to the preserved cluster, the interstitial and emphysema clusters had worse lung function, exercise capacity and quality of life. In longitudinal follow-up, individuals from the emphysema group had greater declines in exercise capacity and lung function, more emphysema, more exacerbations, and higher mortality. Similarly, genes involved in inflammatory pathways (tumor necrosis factor-α, interferon-ß) are more highly expressed in bronchial epithelial cells from individuals in the emphysema cluster, while genes associated with T-cell related biology are decreased in these samples. Samples from individuals in the interstitial cluster generally had intermediate levels of expression of these genes. INTERPRETATION: Using quantitative CT imaging, we identified three groups of individuals in older ever-smokers that replicate in two cohorts. Airway gene expression differences between the three groups suggests increased levels of inflammation in the most severe clinical phenotype, possibly mediated by the tumor necrosis factor-α and interferon-ß pathways. CLINICAL TRIAL REGISTRATION: COPDGene (NCT00608764), DECAMP-1 (NCT01785342), DECAMP-2 (NCT02504697).
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Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Fumar/efectos adversos , Tomografía Computarizada por Rayos X , Centros Médicos Académicos , Anciano , Femenino , Hospitales de Veteranos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/genética , Estados Unidos/epidemiologíaRESUMEN
In-situ ammonium removal from municipal solid waste (MSW) landfill is an attractive method due to its economic advantages. In this study, two simulated MSW bioreactors with different degrees of initial bio-stabilization were utilized to investigate the effects of intermittent aeration mode and the addition of activated sludge on the removal of ammonium. The results showed that up to 90% of ammonium could be removed and the amount of NO(x)-N produced was less than 1% of NH4 (+)-N removed in both reactors. The pH values increased rapidly and finally arrived at a high level of 8.5-8.8. The efficiency of ammonium removal was improved by increasing the continuous aeration time, but it was not affected by the addition of activated sludge. A portion of liquid escaped from the reactors in the form of vapour, and as high as 195-258 mg L(-1) of NH(4) ( +)-N was detected in the vapour collector. According to calculation, nitrification was inhibited by the high level of free ammonia in the bioreactors. As a result, air stripping was enhanced and became the primary pathway of ammonium removal. Therefore, controlling free ammonia concentration was essential in ammonium removal from the aerated MSW bioreactor.