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BACKGROUND: Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms. METHODS: The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway. RESULTS: Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and transforming growth factor-ß1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions. CONCLUSIONS: Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.
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Proteínas Quinasas Activadas por AMP , Fibrosis Pulmonar , Dióxido de Silicio , Simvastatina , Animales , Masculino , Ratas , Acetofenonas/farmacología , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , NADPH Oxidasa 4/metabolismo , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/prevención & control , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Neumonía/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Ribonucleótidos/farmacología , Transducción de Señal/efectos de los fármacos , Silicosis/tratamiento farmacológico , Silicosis/patología , Silicosis/metabolismo , Simvastatina/farmacología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
China has abundant agricultural and forestry waste resources that are crucial sources of energy for substituting fossil fuels and achieving the carbon peaking and carbon neutrality goals. These resources play an essential role in reducing carbon dioxide emissions and promoting sustainable development. This paper presents an estimation of the number of biomass resources that can be used for energy in 2020 by using parameters such as the grass-to-grain ratio coefficient and excretion coefficient. Moreover, the potential for conversion of biomass resources into biomass energy is evaluated by using parameters such as lower heating value and gas production coefficient. Finally, based on the whole life cycle theory, the potential of biomass energy utilization to reduce carbon dioxide emissions and its impact on carbon peaking is calculated. It was found that the total amount of fossil fuels that can be replaced by biomass energy is 256 million tons of standard coal. Utilizing biomass energy can reduce carbon dioxide emissions by approximately 520 million tons, with a peak impact of 4-6% on carbon peaking. The research results presented in this article can provide valuable data to support the promotion of green transformation in various regions. The findings can serve as a useful reference for formulating localized biomass utilization plans and designing effective emission reduction policies.
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Dióxido de Carbono , Combustibles Fósiles , Biomasa , Dióxido de Carbono/análisis , Carbón Mineral , ChinaRESUMEN
The application of the farm biogas project is a perfect measure to deal with the increasingly nervous global climate problem and energy crisis and can support the accomplishment of urgently needed carbon peaking and carbon neutrality effectively. But the poor economic benefits hinder its better development. Thus, this paper aims to enhance the economics of farm biogas projects and explore a win-win model for economic and environmental benefits by studying the economic impact of participation in carbon trading on three types of farm biogas projects. First, economic analysis of farm biogas projects based on life cycle cost is carried out using case analysis. Second, the greenhouse gas emission reductions are calculated and benefits from carbon trading are considered. Then, the economic robustness was tested. Specifically, the economics of all three types of farm biogas projects is improved after carbon trading. The ecological farm biogas project has the best economic performance, with a net present value of $551,689.11, internal rate of return of 49%, and payback period of 2.39 years. In addition, the emission reductions of 5045.79 t CO2e, 7420.28 t CO2e, and 148.41 t CO2e are very significant. Based on these, suggestions for developing farm biogas projects and introducing biogas projects to carbon trading are put forward for the reference of governments and investors when making investments and reforms. According to the result, participation of farm biogas projects in carbon trading can effectively enhance economic benefits and accelerate the achievement of the greenhouse gas emission reduction target which is of great significance to the urgent goal of global green and low-carbon transformation.
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Gases de Efecto Invernadero , Granjas , Biocombustibles , Carbono , ChinaRESUMEN
Interleukin-34 (IL-34) is a cytokine that is involved in the regulation of immune cells, including macrophages, in the tumor microenvironment (TME). Macrophages are a type of immune cell that can be found in large numbers within the TME and have been shown to have a role in the suppression of immune responses in cancer. This mmune suppression can contribute to cancer development and tumors' ability to evade the immune system. Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that target proteins on immune cells that act as "checkpoints," regulating the activity of the immune system. Examples of these proteins include programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). ICIs work by blocking the activity of these proteins, allowing the immune system to mount a stronger response against cancer cells. The combination of IL-34 inhibition with ICIs has been proposed as a potential treatment option for cancer due to the role of IL-34 in the TME and its potential involvement in resistance to ICIs. Inhibiting the activity of IL-34 or targeting its signaling pathways may help to overcome resistance to ICIs and improve the effectiveness of these therapies. This review summarizes the current state of knowledge concerning the involvement of IL-34-mediated regulation of TME and the promotion of ICI resistance. Besides, this work may shed light on whether targeting IL-34 might be exploited as a potential treatment option for cancer patients in the future. However, further research is needed to fully understand the mechanisms underlying the role of IL-34 in TME and to determine the safety and efficacy of this approach in cancer patients.
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BACKGROUND: Qualified reprocessing, of which meticulous channel brushing is the most crucial step, is essential for prevention and control of endoscopy-associated infections. However, channel brushing is often omitted in practice. This study aimed to evaluate the effect of an automated flexible endoscope channel brushing system (AECBS) on improving the quality of endoscope reprocessing. METHODS: This prospective, randomized controlled study was conducted between 24 November 2021 and 22 January 2022âat Renmin Hospital of Wuhan University, China. Eligible endoscopes were randomly allocated to the auto group (channels brushed by AECBS) or the manual group (channels brushed manually), with sampling and culturing after high-level disinfection and drying. The primary end point was the proportion of endoscopes with positive cultures. RESULTS: 204 endoscopes in the auto group and 205 in the manual group were analyzed. The proportion of endoscopes with positive cultures was significantly lower in the auto group (15.2â% [95â%CI 10.7â%-21.0â%]) than in the manual group (23.4â% [95â%CI 17.9â%-29.9â%]). CONCLUSIONS: AECBS could effectively reduce bioburden and improve reprocessing quality of gastroscopes and colonoscopes. AECBS has the potential to replace manual brushing and lower the risk of endoscopy-associated infections, providing a new option for the optimization of reprocessing.
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Colonoscopios , Endoscopios , Humanos , Estudios Prospectivos , Gastroscopios , Desinfección , Contaminación de Equipos/prevención & controlRESUMEN
The multi-renewable energy complementary system (MRECS) is a good plan that can effectively support the accomplishment of carbon peaking and carbon neutrality on schedule and take full advantage of renewable resources in rural areas. This research investigates the techno-economic feasibility of MRECS in rural areas to promote its large-scale implementation. A MRECS with integrated solar, wind, and biomass energy is proposed for a rural economic development zone. First, a scientific evaluation of the potential for renewable resources in rural areas is done. Second, a case study of the Jize Economic Development Zone is applied to examine the optimal MRECS configuration. Finally, an economic evaluation model that takes environmental benefits into account was created based on life cycle costs (LCCs). For the techno-economic analysis, the net present value (NPV), dynamic investment payback period, and internal rate of return (IRR) are also employed. Findings reveal that (1) the Jize Economic Development Zone has considerable development potential due to its abundance of renewable energy resources and ability to plan for 168.42 MW of renewable energy units; (2) to meet the demand for continuous power generation and realize the sensible use of renewable energy, a combination of 10 MW photovoltaic power generation (PV), 25 MW wind power generation (WT), 2 MW biogas power generation (BG), and 1 MW straw direct combustion power generation (SDC) is able to be implemented; (3) the provided renewable energy system can save indirect expenses up to 10.60 million RMB/year, with significant environmental advantages, when compared to grid extension; and (4) the NPV of the dynamic investment reaches RMB 322.44 million after accounting for the environmental advantages in the income of MRECS. The dynamic investment payback period is 6.42 years, and the IRR is 21.44%. According to the findings, the MRECS is economically viable, and capitalizing on the environmental advantages can increase those advantages even more.
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Desarrollo Económico , Energía Renovable , Humanos , Análisis Costo-Beneficio , China , Biocombustibles , CarbonoRESUMEN
Improving carbon emission efficiency (CEE) has emerged as a critical way for Regional Comprehensive Economic Partnership (RCEP) members to promote carbon reduction in the context of climate change mitigation and carbon neutrality. The super-efficiency slacks-based measure (SBM) model, which considers non-desired outputs, is adopted to comprehensively assess the current state and trend of CEE in 15 RCEP countries from a spatio-temporal dynamic perspective, and the global Malmquist-Luenberger (GML) index is coupled to quantify the spatial and temporal differences and dynamic changes. Following that, taking into account the spatial characteristics of CEE, the extended STIRPAT model and the spatial Durbin model are combined to further investigate the primary influencing factors of CEE. It is found that (1) the CEE of RCEP members is generally poor and unevenly distributed in temporal and spatial dimensions, with significant room for improvement and an overall positive spatial autocorrelation; (2) CEE varies considerably among RCEP members, with developed countries far outstripping developing countries in terms of both the current status and trend of CEE; (3) on a dynamic level, the GML index exhibits W-shaped fluctuations, with technological progress acting as the dominant force; and (4) in terms of spillover effects, affluence and economic agglomeration inhibit CEE enhancement, whereas technology level and investment capacity facilitate it. The findings will be useful in developing carbon-neutral plans for various countries as well as coordinated sustainable development for RCEP regions.
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Inversiones en Salud , Condiciones Sociales , Carbono , Cambio Climático , Análisis Espacial , China , Desarrollo Económico , EficienciaRESUMEN
It is vital to determine the changing spatiotemporal patterns and driving factors of green total factor energy efficiency (GTFEE) in order to design scientific policies to promote energy efficiency in the Regional Comprehensive Economic Partnership (RCEP) region. From 2010 to 2019, the super-efficient SBM model and the global Malmquist-Luenberger index provide an appropriate framework for measuring the spatiotemporal evolution of GTFEE and the dynamics of energy productivity in RCEP countries. With the coefficient of variation and the Thiel index, an extensive view of the spatiotemporal variance in GTFEE is offered, taking regional heterogeneity into account. Furthermore, the Tobit model is introduced to investigate the factors influencing the GTFEE of RCEP members, which may address the restricted values of the dependent variable when compared to the least squares regression model. Findings suggest that (1) The GTFEE of RCEP members tends to be low and unevenly distributed spatially and temporally, with much room for improvement. (2) The energy productivity index fluctuates strongly, and the improvement primarily comes from technological progress. (3) The Non-ASEAN region possesses higher GTFEE than the ASEAN region, albeit regional variations are diminishing. (4) In terms of the major factors influencing the regional GTFEE, the non-ASEAN region looks to be distinct from the ASEAN region. The findings shed light on the trends and influencing factors of GTFEE in RCEP and serve as a resource for international energy cooperation and sustainable development.
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Conservación de los Recursos Energéticos , Conservación de los Recursos Naturales , Desarrollo Económico , Eficiencia , Desarrollo Sostenible , ChinaRESUMEN
Background: Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transition (EMT) which aggravates subepithelial fibrosis during the process of airway remodelling and enhances resistance to corticosteroids and bronchodilators in refractory asthma. There is growing evidence that IL-27 modulates airway remodelling, however, the molecular mechanisms involving IL-27 and EMT are poorly understood. The objective of this study was to investigate the effects of IL-27 on ovalbumin (OVA)-challenged asthmatic mice in vivo and TGF-ß1-induced EMT in 16HBE cells in vitro. Methods: Airway inflammation, mucus secretion, and collagen deposition were analysed by conventional pathological techniques. The ratio of Th17 and Th9 cells in the spleen of mice was measured using flow cytometry, ELISA was performed for cytokine analysis to identify EMT-related molecules and signalling pathways, and other molecular and cellular techniques were used to explore the functional mechanism involving IL-27 and EMT. Results: Airway inflammation in asthmatic mice was significantly alleviated by IL-27, with downregulation of RhoA and ROCK, upregulation of E-cadherin, and a decrease of vimentin and α-SMA expression, compared to asthmatic mice. Moreover, the frequency of Th17 and Th9 cells in the spleen of asthmatic mice decreased following treatment with IL-27. In TGF-ß1-induced 16HBE cells, the addition of IL-27 was shown to inhibit EMT, based on the expression of E-cadherin, vimentin, and α-SMA. Conclusion: Intranasal administration of IL-27 attenuates airway inflammation and EMT in a murine model of allergic asthma possibly by downregulating the RhoA/ROCK signalling pathway.
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Asma , Interleucina-27 , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Asma/tratamiento farmacológico , Cadherinas/metabolismo , Cadherinas/farmacología , Cadherinas/uso terapéutico , Transición Epitelial-Mesenquimal/fisiología , Inflamación/tratamiento farmacológico , Ratones , Factor de Crecimiento Transformador beta1/metabolismo , Vimentina/farmacología , Vimentina/uso terapéutico , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
PURPOSE: To elucidate the relationship between peripheral edema and programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, the meta-analysis was performed. METHOD: Following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses, all-grade and grade 3-5 of peripheral edema data extracted from clinical trials were taken into account for the final comprehensive assessments. RESULTS: Twenty-seven PD-1/PD-L1-related clinical trials with peripheral edema data were collected. Compared with chemotherapy (PD-1/PD-L1 vs chemotherapy), the risk of developing peripheral edema for all-grade was much lower (odds ratio [OR] = 0.36, 95% confidence interval [CI]: [0.23, 0.56], Z = 4.55 [P < .00001]). When PD-1/PD-L1 plus chemotherapy were compared with chemotherapy, no significant analysis results for all-grade was found (OR = 1.15, 95% CI:[0.93, 1.44], I2 = 25%, Z = 1.27 [P = .20]). Similar risk trends could also be found when the incidence risk of peripheral edema for grade 3-5 was evaluated. No obvious publication bias was identified throughout the total analysis process. CONCLUSION: The effect of PD-1/PD-L1 inhibitor on the risk of developing peripheral edema was weaker than that of chemotherapy, and the combination with chemotherapy slightly increased the incidence risk of developing peripheral edema without statistical significance.
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Antígeno B7-H1 , Neoplasias , Antígeno B7-H1/uso terapéutico , Edema/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Incidencia , Neoplasias/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/uso terapéuticoRESUMEN
Background: This study was designed to explore the implications of ferroptosis-related alterations in glioblastoma patients. Method: After obtaining the data sets CGGA325, CGGA623, TCGA-GBM, and GSE83300 online, extensive analysis and mutual verification were performed using R language-based analytic technology, followed by further immunohistochemistry staining verification utilizing clinical pathological tissues. Results: The analysis revealed a substantial difference in the expression of ferroptosis-related genes between malignant and paracancerous samples, which was compatible with immunohistochemistry staining results from clinicopathological samples. Three distinct clustering studies were run sequentially on these data. All of the findings were consistent and had a high prediction value for glioblastoma. Then, the risk score predicting model containing 23 genes (CP, EMP1, AKR1C1, FMOD, MYBPH, IFI30, SRPX2, PDLIM1, MMP19, SPOCD1, FCGBP, NAMPT, SLC11A1, S100A10, TNC, CSMD3, ATP1A2, CUX2, GALNT9, TNFAIP6, C15orf48, WSCD2, and CBLN1) on the basis of "Ferroptosis.gene.cluster" was constructed. In the subsequent correlation analysis of clinical characteristics, tumor mutation burden, HRD, neoantigen burden and chromosomal instability, mRNAsi, TIDE, and GDSC, all the results indicated that the risk score model might have a better predictive efficiency. Conclusion: In glioblastoma, there were a large number of abnormal ferroptosis-related alterations, which were significant for the prognosis of patients. The risk score-predicting model integrating 23 genes would have a higher predictive value.
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Rapid urban expansion and energy transformation are two major challenges facing China. Many researchers have explored urban compactness and energy efficiency, but there is little literature on the coordinated development of the two. Therefore, this paper takes 35 cities in China as research object: The urban compactness evaluation index system is established, and the score is calculated using the entropy weight method; considering the bad output, SBM is used to calculate the green total factor energy efficiency (GTFEE); and the coupling coordination degree model is used to calculate their coordinated degree. The following conclusions can be inferred: (1) Although China's urban compactness has increased, it has not maintained a steady upward trend. Some more developed cities have the phenomenon of compactness rising first and then falling; (2) The overall GTFEE shows a continuous upward trend, but there is still much room for improvement, and regional disparities are significant; (3) The degree of coordination between the two maintains a steady upward trend, and the city's compactness lags behind GTFEE. Based on the findings of the study, this paper proposes policy recommendations that can serve as a reference for key decision-makers and are critical in promoting China's urbanization and energy transformation.
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Conservación de los Recursos Energéticos , Desarrollo Económico , China , Ciudades , Eficiencia , UrbanizaciónRESUMEN
The biological functional network of tumor tissues is relatively stable for a period of time and under different conditions, so the impact of tumor heterogeneity is effectively avoided. Based on edge perturbation, functional gene interaction networks were used to reveal the pathological environment of patients with non-small cell carcinoma at the individual level, and to identify cancer subtypes with the same or similar status, and then a multi-dimensional and multi-omics comprehensive analysis was put into practice. Two edge perturbation subtypes were identified through the construction of the background interaction network and the edge-perturbation matrix (EPM). Further analyses revealed clear differences between those two clusters in terms of prognostic survival, stemness indices, immune cell infiltration, immune checkpoint molecular expression, copy number alterations, mutation load, homologous recombination defects (HRD), neoantigen load, and chromosomal instability. Additionally, a risk prediction model based on TCGA for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was successfully constructed and validated using the independent data set (GSE50081).
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Humanos , Neoplasias Pulmonares/patología , PronósticoRESUMEN
BACKGROUND: Novel coronavirus disease (COVID-19) is a kind of pulmonary inflammation induced by New Coronavirus. It seriously threatens people's health and safety. Clinical studies have found that some patients have different degrees of inflammation after discharge from hospital, especially in patients with severe inflammatory lung fibrosis. Early combination of Chinese medicine and modern medicine has important clinical significance. There are still many deficiencies in the current research. We studied the effectiveness of the combination of traditional Chinese medicine and modern medicine in the treatment of pulmonary fibrosis caused by COVID-19, and proposed a network meta-analysis (NMA) scheme. METHODS: According to the search strategy, we will search Chinese and English databases to collect all randomized controlled trials of traditional Chinese medicine combined with modern drugs or only using traditional Chinese medicine for new coronavirus-19-induced pulmonary fibrosis between December 1, 2019 and November 15, 2021. First, the literature was screened according to the eligibility criteria, endnotex9 was used to manage the literature, and the Cochrane Collaboration's tool was used to assess the quality of the included literature. Revman 5.3, Stata 14.2, and gemtc14.3 meta-analysis software was then used for data processing and analysis, and the grading of recommendations assessment will be used to develop and evaluate a hierarchy for classifying the quality of evidence for NMA. RESULTS: Through the analysis, the ranking of efficacy and safety of various treatments for pulmonary fibrosis caused by COVID-19 will be drawn, thus providing stronger evidence support for the choice of clinical treatment methods. CONCLUSION: Traditional Chinese medicine (TCM) combined with modern drugs has played a positive role in the treatment of pulmonary fibrosis caused by COVID-19, and this study may provide more references for the clinical medication of pulmonary fibrosis caused by COVID-19. INPLASY REGISTRATION NUMBER: INPLASY2021110061.
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Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos , Fibrosis Pulmonar , Teorema de Bayes , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Medicina Tradicional China , Metaanálisis como Asunto , Metaanálisis en Red , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Carbon emission efficiency directly determines the level of green economic development. Based on the panel data of China's Yangtze River Economic Belt (YEB) from 2008 to 2017, this paper uses the stochastic frontier analysis (SFA) model to analyze the overall carbon emission efficiency level, influencing factors, and changing trends, with a view to discussing the relationship between economic development and carbon emission efficiency. The results suggest, first, the overall carbon emission efficiency of the YEB is on an upward trend, but there is still much room for improvement. Second, the impact of industrialization and urbanization on carbon emission efficiency follows a U-shaped. As industrialization and urbanization progress, the impact on carbon emission efficiency shows a downward and then upward trend. Third, due to the rebound effect, technological progress has a slight negative impact on carbon emission efficiency. Energy consumption structure, government intervention, and foreign trade are all negative incentive factors. Therefore, efforts to improve carbon emission efficiency in the YEB should focus on transforming the economic growth model, adjusting the industrial structure, improving the energy consumption structure, and innovating green technology. The research results can provide a reference for the government policymakers to develop a green economy.
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Ríos , Urbanización , Carbono/análisis , China , Desarrollo Económico , Eficiencia , Desarrollo IndustrialRESUMEN
Increased number of airway smooth muscle cells (ASMCs) is a characteristic of airway remodeling in asthma. In this study we investigated whether emodin alleviated airway remodeling in a murine asthma model and reduced the proliferation of ASMCs in vitro. We provided in vivo evidence suggesting that intraperitoneal injection of emodin (20 mg/kg) 1 h prior to OVA challenge apparently alleviated the thickness of airway smooth muscle, the mass of alpha-smooth muscle actin (α-SMA), collagen deposition, epithelial damage, goblet cell hyperplasia, airway inflammation and airway hyperresponsiveness (AHR) in lung tissue. Meanwhile, we found that emodin suppressed the activation of the Akt pathway in lungtissue of allergic mouse models. Additionally, we found that emodin inhibited cellular proliferation and Akt activation in a dose-dependent manner in vitro. Furthermore, LY294002, an inhibitor for PI3K, abrogated serum-induced phosphorylation of Akt, and decreased the proliferation of ASMCs. These findings indicated that emodin alleviated ASMCs proliferation by inhibiting PI3K/Akt pathway in vivo and in vitro, which may provide a potential therapeutic option for airway smooth muscle remodeling in asthma.
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Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Emodina/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Actinas/biosíntesis , Actinas/efectos de los fármacos , Animales , Asma/inducido químicamente , Asma/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar/inmunología , Células Cultivadas , Colágeno/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Emodina/uso terapéutico , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Femenino , Células Caliciformes/efectos de los fármacos , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos BALB C , Miocitos del Músculo Liso/citología , Ovalbúmina/toxicidad , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hipersensibilidad Respiratoria/tratamiento farmacológico , Células Th2/metabolismoRESUMEN
Type 2 cytokineassociated immunity may be involved in the pathogenesis of allergic asthma. Although interleukin 27 (IL27) has been reported as an initiator and suppressor of Thelper 1 (Th1) and Thelper 2 (Th2) responses, respectively, its effects on the development of asthma remain unclear. In the present study, mice were induced and challenged with ovalbumin and received subsequent intranasal administration of IL27. Total and differential cell counts were determined from WrightGiemsastained cytospins, whereas the cytokine levels were detected using ELISA. In addition, the expression levels of signal transducer and activator of transcription (STAT) 1, STAT3, GATAbinding protein3 (GATA3) and Tbet (Tbox transcription factor) were analyzed in T cells by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PCR. Airway remodeling was assessed by conventional pathological techniques. The results indicated that intranasal administration of IL27 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Furthermore, IL27 prevented airway remodeling in a chronic model of asthma. Following administration of IL27, the mRNA expression levels of STAT1 and Tbet were upregulated, while those of GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrated that intranasal administration of IL27 ameliorated Th2related allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT3 pathways.
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Asma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Interleucina-27/farmacología , Interleucina-27/uso terapéutico , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismo , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Animales , Asma/metabolismo , Lavado Broncoalveolar , Ensayo de Inmunoadsorción Enzimática , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/metabolismo , Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Amide proton transfer-weighted (APTw) imaging has been revealed to hold great potential in the diagnosis of several brain diseases. The purpose of this proof-of-concept study was to evaluate the feasibility and value of APTw magnetic resonance imaging (MRI) in characterizing normal brain aging. METHODS: A total of 106 healthy subjects were recruited and scanned at 3.0 Tesla, with APTw and conventional magnetization transfer (MT) sequences. Quantitative image analyses were performed in 12 regions of interest (ROIs) for each subject. The APTw or MT ratio (MTR) signal differences among five age groups (young, mature, middle-aged, young-old, and middle-old) were assessed using the one-way analysis of variance, with the Benjamini-Hochberg correction for multiple comparisons. The relationship between APTw and MTR signals and the age dependencies of APTw and MTR signals were assessed using the Pearson correlation and non-linear regression. RESULTS: There were no significant differences between the APTw or MTR values for males and females in any of the 12 ROIs analyzed. Among the five age groups, there were significant differences in the three white matter regions in the temporal, occipital, and frontal lobes. Overall, the mean APTw values in the older group were higher than those in the younger group. Positive correlations were observed in relation to age in most brain regions, including four with significant positive correlations (r=0.2065-0.4182) and five with increasing trends. As a comparison, the mean MTR values did not appear to be significantly different among the five age groups. In addition, the mean APTw and MTR values revealed significant positive correlations in 10 ROIs (r=0.2214-0.7269) and a significant negative correlation in one ROI (entorhinal cortex, r=-0.2141). CONCLUSIONS: Our early results show that the APTw signal can be used as a promising and complementary imaging biomarker with which normal brain aging can be evaluated at the molecular level.
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Purpose: Airway remodeling is one of the features of severe asthma. Previous study shows that IL-27 inhibits airway inflammation in asthmatic mice. However, the role of IL-27 on airway remodeling in OVA-induced asthmatic mice and its possible mechanism remain unclear. Methods: We established an ovalbumin (OVA)-induced asthmatic mice model. IL-27 were preventative administered to OVA-induced asthmatic mice. The total cells in Bronchoalveolar lavage fluid (BALF) and Airway hyperresponsiveness (AHR) were measured. The lung tissues were performed by Hematoxylin and eosin (HE) staining to estimate the pathological changes. Masson staining was used to observe the collagen deposition area. The expression of α-smooth muscle actin (α-SMA) and Type I collagen was measured by immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Additionally, western blot was also used to measure the expression of phosphorylated-Akt (p-Akt) in each group. Results: IL-27 group showed significant inhibitory effect on the α-SMA and Type I collagen. The expression of p-Akt in the tissues of asthma model was increased and inhibited by IL-27. Conclusions: IL-27 can alleviate airway remodeling in OVA-induced asthmatic mice, and the mechanism may relate to PI3K/Akt pathway.