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Emerging studies have reported the mechanosensitive Piezo1 (piezo type mechanosensitive ion channel component 1) plays essential roles in regulating the vascular tone through mechanistic actions on intracellular calcium homeostasis. However, the specific roles of Piezo1 in pulmonary vessels remain incompletely understood. We aim to investigate whether and how Piezo1 regulates the intracellular calcium homeostasis in human pulmonary arterial smooth muscle cells (PASMCs) under normal and pulmonary arterial hypertension (PAH) conditions. Cultured human PASMCs isolated from both control donors and idiopathic PAH patients were used as cell models. Fura-2 based intracellular calcium imaging was performed to measure the intracellular free calcium concentration ([Ca 2+ ] i ). Results showed that activation of Piezo1 by Yoda1 increases [Ca 2+ ] i by inducing both intracellular calcium release from internal calcium stores through the intracellular (intra-) Piezo1 localized at the subcellular organelles, including endoplasmic reticulum/sarcoplasmic reticulum, mitochondria, and nucleus; as well as extracellular calcium influx through the plasma membrane-localized Piezo1 in a mechanism independent of the store-operated calcium entry. Moreover, the Piezo1-mediated increase of [Ca 2+ ] i is linked to increased contraction and proliferation of PASMCs. Yoda1 induces dose-dependent vasocontraction in endothelium-denuded rat intrapulmonary arteries. Significant upregulation and increased activity of Piezo1 were observed in idiopathic PAH-PASMCs versus donor-PASMCs, contributing to the increased [Ca 2+ ] i and excessive proliferation of idiopathic PAH-PASMCs. In summary, Piezo1 mediates the increase of [Ca 2+ ] i by triggering both intracellular calcium release and extracellular influx. The enhanced Piezo1 expression and activity accounts, at least partially, for the abnormally elevated [Ca 2+ ] i and proliferation in idiopathic PAH-PASMCs.

Reactive atmosphere significantly affects pyrolysis of biomass, as the gases such as NH3 involves in the reaction network in pyrolysis. In this study, instead of feeding reactive gas, the impacts of co-feeding ethanol or glycol on the pyrolysis of cellulose were investigated at varied pyrolysis temperatures (400 and 600 °C). The results showed that the co-feeding of the alcohols affected yields of bio-char and tar, evolution of light organics and heavy organics, elemental composition, formation of fused ring structures, crystallinity, thermal stability, distribution of functionalities in the bio-char. The co-feeding of both glycol and ethanol enhanced the formation of the heavy components with the π-conjugated ring structures and affected the production of the light organics such as furfural and glycolaldehyde. Glycol or its derivatives cross-polymerized with the organics in bio-char, increasing bio-char yield and made the bio-char more oxygen-rich. Ethanol, however, showed the converse effects. Co-feeding of the alcohols promoted crystallinity but showed distinct effects on thermal stability of the bio-char at the varied pyrolysis temperatures. Both pyrolysis temperature and structures of the alcohols determined their extents of involvement in the pyrolysis of cellulose.

Background and purpose Pulmonary hypertension related to pulmonary fibrosis is classed as WHO Group III, one of the most common groups which lacks effective treatment options. In this study, we aimed to uncover the underlying mechanisms, particularly the involvement of the BMP9/BMPR2/SMAD signalling pathway, in this subtype of pulmonary hypertension. Experimental approach Male Sprague Dawley rats were used to establish a model of pulmonary hypertension with pulmonary fibrosis, induced by bleomycin. Haemodynamic and lung functions were measured, along with histological and immunohistochemical examinations. Primary cultures of rat pulmonary microvascular endothelial cells (PMVECs) were analysed with western blots, apoptosis assays and immunohistochemistry. Key results Early (7 days) after bleomycin treatment of rats, pulmonary arterial thickening and severe loss of pulmonary arterial endothelium were observed, followed (14 days) by increased right ventricular systolic pressure and right ventricular hypertrophy. Marked down-regulation of the BMP9/BMPR2/SMAD signalling pathway was markedly down-regulated in lung tissues from bleomycin-treated rats (throughout the 7- to 35-day treatment period) and bleomycin-treated rat PMVECs, along with excessive cell apoptosis and loss of pulmonary arterial endothelium. Treatment with recombinant human bone morphogenetic protein 9 (rhBMP9) attenuated these aspects of bleomycin-induced pulmonary hypertension, by restoring disrupted BMP9/BMPR2/SMAD signalling. Conclusion and implications In bleomycin-treated rats, early and persisting suppression of the BMP9/BMPR2/SMAD signalling pathway triggered severe loss of pulmonary arterial endothelium and subsequent pulmonary arterial vascular remodelling, contributing to the development of pulmonary hypertension. Therapeutic approaches reinforcing BMP9/BMPR2/SMAD signalling might be ideal strategies for this subtype of pulmonary hypertension. Linked articles This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.

Reaction atmosphere is one of the principle parameters affecting pyrolysis characteristics of biomass. In this study, instead of feeding reactive gases, methanol was co-fed in the pyrolysis of saw dust, aiming to understand the impacts of methanol on evolution of functionalities/structures of the major pyrolysis products. The results showed that at low pyrolysis temperature of 350 °C, methanol did not affect much on the charring reactions but promoted the formation of the heavier organics. At 500 or 650 °C, the co-feeding of methanol enhanced the yields of both char and the heavy components of bio-oil, resulting from the reaction of methanol or its derivatives with the organic components on surface of biochar via recombination/condensation reactions. In addition, methanol enhanced evolution of the organics with π-conjugated structures. The co-feeding of methanol also enhanced crystallinity and sizes of the crystal carbon in the biochar, but led to their lower thermal stability. The in situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) characterization of saw dust pyrolysis indicated that methanol promoted the aliphatic structures formation on surface of the biochar, leading to the low thermal stability.

This study investigated the effects of a series of additives ranging from alkali, alkali earth, transition and rare earth metals (Na, Mg, K, Ca, Sc, Cr, Mn, Fe, Co, Cu, Zn, Zr, La, Ce) on catalytic behaviors of Ni/Al2O3 in steam reforming of acetic acid. The addition of alkali and alkaline metals led to the sintering of alumina and nickel species. Cr, Ce or Zr addition filled pores, while Mn addition enhanced the specific area by creating more pores. Cu and Zn addition probably led to merging of small pores. In addition, K or Na promoted reduction of nickel oxides, promoting the catalytic activity. La, Ce or Co also enhanced activity of the catalysts, while Mg, Ca, Sc, Cu, Zn or Zr decreased the activities. The K or Na modified catalysts was much more stable than that of the La or Ce modified catalysts, although the coking was more serious. The coke formed in K or Na modified catalysts was mainly in fibrous form (probably the catalytic coke), while that in La or Ce modified catalysts was mainly amorphous form (probably the polymeric coke). The fibrous coke did not lead to the fast deactivation of the nickel catalysts as the amorphous coke did. The TG-MS and DRIFTS study showed that the coke contained the aliphatic structures with the functionalities such as methyl group, carbonyl groups, carboxylic structures as well as the structures of aromatic rings. The amorphous coke formed in La or Ce modified catalysts contained more aliphatic structures. The in situ DRIFTS study of steam reforming of acetic acid showed that a number of reaction intermediates including the –OH, C O, aliphatic C C, aromatic C C, COO, C–H, –CH3, aliphatic C–O–C structure, and absorbed CO2 involved in the reforming reaction.

Reaction atmosphere is one of the principle reaction parameters affecting the pyrolysis of biomass. At elevated temperatures, in addition to gases, organics are also regarded as part of the reaction atmosphere. In this study, the impacts of the co-feeding of formic acid or acetic acid on the pyrolysis behaviour of cellulose were investigated at 400 and 600 °C, respectively. The results showed that the co-feeding of the acids significantly affected properties of both the resulting bio-oil and biochar. Co-feeding of acetic acid remarkably promoted formation of heavier organics with π-conjugated structures, while the presence of formic acid suppressed their evolution, especially at the lower pyrolysis temperature of 400 °C. The co-feeding of the carboxylic acids increased the yields of biochar. Furthermore, the co-feeding of formic acid or acetic acid also affected the elemental composition, the defective structure, the crystallinity and the thermal stabilities of the resulting biochar at varied pyrolysis temperature in the distinct ways. The carboxylic acids or their derivatives interfered with the formation of the volatiles or reacted directly with the organic components on surface of biochar, which substantially modified the physiochemical properties of the biochar.

Metal oxides are frequently used in the formulations of the catalysts for catalytic pyrolysis of biomass. This study aims to investigate the catalytic behaviors of the transition metal oxides (CoO, Cr2O3, CuO, Fe2O3, Mn2O3, NiO, TiO2 and V2O5) as well as CeO2 for the catalytic pyrolysis of poplar wood. The metal oxides, especially TiO2 and NiO could suppress further cracking of primary products, increasing the tar yield and simultaneously decreasing the gas yield. The V, Mn, Ti or Co-based catalyst promoted the formation of the heavy bio-oil, while the Ce, Cr, Cu or Fe-based catalysts were the opposite. The metal oxides (except Fe2O3) promoted the formation of alcohols, furan, ketones, acetic acid and phenolics in bio-oil. Fe2O3 catalysts suppressed formation of the derivatives from cellulose and hemicellulose except hydroxyl acetone. Hydroxyl acetone formation was promoted by almost all the oxide catalysts while hydroxyl aldehyde formation was the opposite. Remarkable coke formed over the V, Mn, Cu and Co-based catalysts. These oxides contain multiple valences and could be partially reduced to generate oxygen vacancies, which played important roles in the polymerisation reactions. In addition, the coke species formed on the oxide catalysts were mainly polymeric with low thermal stability.

In this study, the potential of attapulgite (ATTP) as the support of nickel catalysts for steam reforming of acetic acid to produce hydrogen were evaluated. Ni/Al2O3 was prepared and evaluated for comparison. The results showed that ATTP had a much lower specific surface area and a lower thermal stability than alumina. Nevertheless, the interaction between nickel and ATTP was much weaker than that of nickel with alumina. As a result, the Ni/ATTP catalyst had superior activity than the Ni/Al2O3 catalyst, especially at low nickel loading. Ni/Al2O3 was more stable than Ni/ATTP. The fibrous coke, which was probably catalytic coke, formed over Ni/Al2O3 did not cause the rapid deactivation of the catalyst, while the amorphous coke formed over Ni/ATTP catalyst, which was probably the polymeric coke, rapidly deactivated the catalyst. The coke species contained COOH, C O, aliphatic structure and aromatic ring structures. In addition, the effects of these two carriers on the steam reforming mechanism were investigated by the in-situ DRIFTS.

Polyethylene is a major contributor of plastic waste, which can be converted into liquid fuel via catalytic pyrolysis. In this study, the pyrolysis of light or heavy density polyethylene (LDPE and HDPE) and their mixture with the biochar produced from gasification of poplar wood as catalyst was investigated. The results showed that, during the co-pyrolysis of LDPE and HDPE in absence or presence of biochar catalyst, cross-interaction of reaction intermediates originated from the degradation of LDPE and HDPE substantially promoted the formation of gaseous products and the evolution of heavy organics with π-conjugated structures in the tar. During the pyrolysis of HDPE, more heavy tar while less wax was produced, while it was contrary during the pyrolysis of LDPE. In the catalytic pyrolysis of LDPE, the volatiles could be effectively cracked over the biochar catalyst, forming more gases, while in the catalytic pyrolysis of HDPE, instead of catalyzing the cracking of the heavy components, the biochar catalyzed the polymerisation reactions. The properties of the biochar catalyst in terms of crystallinity, surface functionality, and internal structures also changed remarkably due to the transfer of oxygen-containing species from the polyethylene to biochar and the interaction of biochar with volatiles in the pyrolysis.

Tire scrap is a solid waste that can be potentially used as the feedstock for the production of liquid fuels via the thermochemical process such as catalytic pyrolysis. Nevertheless, it remains challenging to develop the efficient while cost-effective catalyst for the catalytic pyrolysis of tire. In this study, the pyrolysis of tire scrap at 500 °C with the biochar produced from the gasification of poplar wood at 850 °C were conducted. The biochar catalyst significantly affected the evolution of the volatiles and the char properties, while had a slight impact on the yields of the gas, tar and char products. The biochar catalyst catalyzes the cracking of limonene, a major liquid product in tar, to form significantly more propane in gases and alkanes or alkenes in the tar. In addition, the interaction between the biochar with the oxygen-containing organics promoted the re-condensation reaction, which increased the oxygen content in the char, but the biochar catalyst did not influence the evolution of the aromatics. Additionally, the catalytic pyrolysis also makes the biochar catalyst more oxygen-deficient and more resistant towards oxidation. Concluding all the results showed that biochar, which were produced from the gasification of poplar wood can be a potential catalyst for the pyrolysis of tire.

This study investigated the interaction of nickel species with alumina versus calcination temperature and nickel loading. A total of 22 Ni/Al2O3 catalysts, calcined at the temperature from 500 to 1000 °C at a 50 °C increment, were employed for the study. High calcination temperature led to the formation of nickel–alumina spinel via the solid phase reaction, which shifted the reduction temperature to higher ranges. The catalyst, however, still achieved good activity after full reduction of the nickel–alumina spinel. Nevertheless, the high calcination temperature led to the collapse of the small pores and the formation of the big one, resulting in the significant decrease of specific surface area. At higher nickel loadings, more nickel species weakly interacted with alumina formed as the reactive center of alumina was saturated. With the increase of nickel loading, the catalytic activities were not varied much but the catalytic stability and the resistivity towards coking enhanced. The coke produced over the catalyst at low nickel loading tended to be amorphous, while the coke produced at the high nickel loading was more fibrous. Furthermore, the coke produced at the low loading contained more small aromatic rings and more oxygen-containing functional groups. The higher nickel loading possibly promoted the catalytic cracking reactions to form more catalytic coke while the low nickel loading probably favored the polymerization reactions to form the polymeric coke. In addition, the calcination at the higher temperature could enhance the stability of the catalysts, which might be related to the enlarged pore sizes.

This study investigated the effects of the acidity/alkalinity of seven oxides (Al2O3, SiO2, ZnO, K2O, MgO, CaO, La2O3) on the pyrolysis of poplar, cellulose and lignin. The results showed that the basic supports such as CaO and MgO promoted the formation of gaseous products. CO, CO2, and CH4 were the main gaseous products in the pyrolysis of poplar, cellulose and lignin, and CO was formed first, followed by CO2 and CH4. Some H2 was also formed from the dehydrogenation reactions over CaO with cellulose as the feedstock. The acidic oxides promoted the tar formation, while the basic oxides suppressed tar formation. The oxides like CaO could remarkably suppress the production of phenolic compounds. The coke formation over the basic oxides were also much more significant than that over the acidic oxides, and the tar from cellulose contributed more towards coking. The heating of the coke in inert gas released CO2, CO, H2, CH4 via probably decarboxylation/decarbonylation, dehydrogenation and etc. The coke from the pyrolysis of lignin was much more stable. CaO and La2O3 reacted with the CO2 produced in pyrolysis and form the carbonates, while MgO could not. The TPO–MS characterization showed that the coke species were multiple types over CaO, and a single type over MgO. The cellulose–derivatives and the lignin–derivatives have distinct effects on the structural configuration of the coke.

This study investigated the pyrolysis of lignin pyrolysis in a temperature region from 200 to 800 °C, aiming to understand influence of pyrolysis temperature on evolution of structures of the resulting char. The results showed that fusion of the ring structure initiated at 200 °C, where the C/H ratio in the char was equal to that in naphthalene (two fused rings). The C/H ratio in the char obtained at 350 °C corresponded to that in pyrene (four fused rings), while the char produced at 550 °C was equivalent to 20 fused benzene rings in terms of C/H ratio. The increasing pyrolysis temperature also shifted the oxygen-containing functionalities such as the carbonyl, esters, ketones in the bio-oil to the ether functionality that had a higher thermal stability. The DRIFTS study of pyrolysis of lignin showed that drastic changes of the functionalities and the internal structure of the char occurred in a narrow temperature region from 520 to 530 °C. The carbonyl functionality and the aliphatic structure were eliminated, and new conjugated π-bond systems formed.

For decades, stem cell therapies for pulmonary hypertension (PH) have progressed from laboratory hypothesis to clinical practice. Promising preclinical investigations have laid both a theoretical and practical foundation for clinical application of mesenchymal stem cells (MSCs) for PH therapy. However, the underlying mechanisms are still poorly understood. We sought to study the effects and mechanisms of MSCs on the treatment of PH. For in vivo experiments, the transplanted GFP(+) MSCs were traced at different time points in the lung tissue of a chronic hypoxia–induced PH (CHPH) rat model. The effects of MSCs on PH pathogenesis were evaluated in both CHPH and sugen hypoxia–induced PH models. For in vitro experiments, primary pulmonary microvascular endothelial cells were cultured and treated with the MSC conditioned medium. The specific markers of endothelial-to-mesenchymal transition (EndMT) and cell migration properties were measured. MSCs decreased pulmonary arterial pressure and ameliorated the collagen deposition, and reduced the thickening and muscularization in both CHPH and sugen hypoxia–induced PH rat models. Then, MSCs significantly attenuated the hypoxia-induced EndMT in both the lungs of PH models and primary cultured rat pulmonary microvascular endothelial cells, as reflected by increased mesenchymal cell markers (fibronectin 1 and vimentin) and decreased endothelial cell markers (vascular endothelial cadherin and platelet endothelial cell adhesion molecule-1). Moreover, MSCs also markedly inhibited the protein expression and degradation of hypoxia-inducible factor-2α, which is known to trigger EndMT progression. Our data suggest that MSCs successfully prevent PH by ameliorating pulmonary vascular remodeling, inflammation, and EndMT. Transplantation of MSCs could potentially be a powerful therapeutic approach against PH.

The pyrolysis of cellulose at 200–800 °C with an increment of 50 °C was conducted in this study, aiming to understand impacts of temperature on evolution of the of organics and the structures of bio-char. Extensively pyrolysis of cellulose to bio-oil initiated at 300 °C, reached maximum at 450 °C, and shifted to gasification to produce gases as the main products above 650 °C. Dehydrate sugars were the initial products formed below 350 °C, which soon dehydrated to form furans at ca. 400 °C and then generate aliphatic aldehydes, ketones and carboxylic acids at ca. 650 °C via the session of the C–C bonds. Aromatization of the volatiles initiated at 350 °C, producing phenolics and then further to aromatic hydrocarbons. The medium pyrolysis temperature (i.e. 450 °C) tended to produce the heavier bio-oil. The in situ DRIFTS characterization of cellulose pyrolysis showed that the structural reconstruction of the feedstock occurred at ca. 430–440 °C, forming abundant C O functionalities in bio-char. The increasing pyrolysis temperature led to staged change of carbon, hydrogen and oxygen contents in bio-char. The bio-char produced at the low temperature was quite aliphatic, and increasing pyrolysis temperature enhanced the formation of graphite structure, thermal stability and the porosity of bio-char. The bio-char from cellulose had a compact structure with small surface area and very limited mesopores. The results of kinetic analysis showed that the pyrolysis of cellulose was a complex multi-step reaction process.

In this study, the co-pyrolysis of pig manure with cellulose and glucose were investigated at various heating rates. The results demonstrated that potential cross-interaction of the volatiles from the co-pyrolysis facilitated the cracking reaction, resulted in the formation of less charry products and less tarry compounds in the co-pyrolysis. The volatiles interaction also enhanced the evolution of the organics with the π-conjugated ring structures in the bio-oil and remarkably affect the char properties. The dehydration and condensation reactions were promoted during the fast co-pyrolysis of manure with cellulose and glucose, leading to the increased carbon content (from 20.0%–46.5 and 43.0 %), the higher thermal stability, and the enhanced crystallinity of carbon structure in the char formed. In addition, the in-situ Diffuse Reflection Infrared Fourier Transform Spectroscopy (DRIFTS) characterization indicates that the interaction of volatiles in the co-pyrolysis obviously affected the evolution of the functionalities of the char and the reaction network. Additionally, the HHV (37.2 and 37.9 vs 28.0 MJ/Kg) and the energy yield (66.3 and 68.2 vs 66.2 %) of the char from the co-pyrolysis was higher than that of the manure, which was beneficial for the utilize of the char as solid fuel.

The extracted herbal residue, an agricultural waste, was pyrolyzed to produce value-added products by exploring the impact of extraction pretreatment on the pyrolysis performance of herbal feedstock. The Artemisia capillaris thumb, a kind of Chinese herbal medicine, was extracted with ethanol to get the herbal waste. The herbal residue and herbal feedstock were pyrolyzed at different pyrolysis temperature. The results showed the extraction of the herb with ethanol affected both the yields and composition/properties of bio-oil/biochar. Extraction of the herb also affected the pyrolysis of cellulose, hemicellulose or lignin in distinct ways. Compared with the extracted herbs, the yield of ketones, acids and furans in bio-oils produced by herb pyrolysis at 300 °C was higher than 11, 14 and 41%, respectively, which belonged to the derivates from the cellulose component or hemicellulose component. However, when the herb was pyrolyzed at 500 °C, it was compared with when the extract herb was pyrolyzed at 500 °C that the yield of the phenolics with monocyclic ring or fused ring structures in the bio-oil was lower than 3%. According to the DRIFTS analysis, the evolution of the carbonyl-containing organics during the pyrolysis was also affected by the extraction of the herb. As for the char, more carbonyl group was retained in the char from the extracted herb. Nevertheless, the results from thermal analysis showed that thermal stability of the char from extracted herb was remarkably lower than that from herb feedstock.

Pyrolysis temperature is one of the main parameters affecting the properties of biochar and the composition of bio-oil during the pyrolysis of aquatic biomass such as seaweed. In this study, the evolution of the functional groups of biochar during seaweed pyrolysis was characterized with in situ diffuse reflectance infrared Fourier transform spectroscopy. The results showed that restructuring of the biochar was more pronounced at temperatures ranging from 230 to 290 °C, where the decomposition and pyrolysis of glucose crystals, polysaccharides and long-chain aliphatic compounds dominated. Fusion of the aromatic rings started and reached the equivalent of six fused rings at 500 °C and 12 fused benzene rings at 800 °C. Varying the pyrolysis temperature remarkably affected the distribution/transformation of the heteroatom in biochar and in the bio-oil formed. A large proportion of nitrogen in the original protein formed in seaweed was retained in the biochar, even at 800 °C. The sulfur species in the original sulfate polysaccharide form was transformed initially to Mg2K2(SO4)3 and then to MgO and CaS crystals. The oxygen content in the seaweed-derived biochar was rather high, as a significant portion of carbon was transferred into the tar fraction due to the aliphatic nature of seaweed.

This study studied the change of functionalities in the biochar formed in pyrolysis of poplar wood in a wide range of temperature. The in situ Diffuse Reflectance Infrared Fourier transform spectroscopy characterization indicated that aldehydes and ketones functionalities formation initiated at 100 °C, dominated at 300 to 500 °C. Carboxyl group was less stable than carbonyls. Cellulose crystal in poplar decomposed slightly at 300 °C and significantly at 350 °C. The temperature from 250 to 350 °C significantly affected biochar yields, while the drastic fusion of the ring structures in biochar occurred from 550 to 650 °C, making biochar more aliphatic while less more aromatic. High pyrolysis temperature also created more defective structures in the biochar and favored the absorption of the CO2 generated during the pyrolysis. The results provide the reference information for understanding the structural configuration and evolution of the functionalities during in pyrolysis of poplar biomass.

Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α–induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD.

NEW FINDINGS What is the central question of this study? In this study, by using motor vehicle exhaust (MVE) exposure with or without lipopolysaccharide (LPS) instillation, we established, evaluated and compared MVE, LPS and MVE+LPS treatment-induced chronic obstructive pulmonary disease (COPD) models in mice. What is the main finding and its importance? Our study demonstrated that the combination of chronic exposure to MVE with early LPS instillation can establish a mouse model with some features of COPD, which will allow researchers to investigate the underlying molecular mechanisms linking air pollution and COPD pathogenesis. ABSTRACT Although it is well established that motor vehicle exhaust (MVE) has a close association with the occurrence and exacerbation of chronic obstructive pulmonary disease (COPD), very little is known about the combined effects of MVE and intermittent or chronic subclinical inflammation on COPD pathogenesis. Therefore, given the crucial role of inflammation in the development of COPD, we wanted to establish an animal model of COPD using both MVE exposure and airway inflammation, which could mimic the clinical pathological changes observed in COPD patients and greatly benefit the study of the molecular mechanisms of COPD. In the present study, we report that mice undergoing chronic exposure to MVE and intratracheal instillation of lipopolysaccharide (LPS) successfully established COPD, as characterized by persistent air flow limitation, airway inflammation, inflammatory cytokine production, emphysema and small airway remodelling. Moreover, the mice showed significant changes in ventricular and vascular pathology, including an increase in right ventricular pressure, right ventricular hypertrophy and remodelling of pulmonary arterial walls. We have thus established a new mouse COPD model by combining chronic MVE exposure with early intratracheal instillation of LPS, which will allow us to study the relationship between air pollution and the development of COPD and to investigate the underlying molecular mechanisms.

Previously, we and others have demonstrated that activation of peroxisome proliferator-activated receptor γ (PPARγ) by specific pharmacological agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH) by suppressing the proliferation and migration in distal pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial effects of PPARγ are mediated by targeting the intracellular calcium homeostasis and store-operated calcium channel (SOCC) proteins, including the main caveolae component caveolin-1. However, other than the caveolin-1 targeted mechanism, in this study, we further uncovered a caveolin-1 dependent mechanism within the activation of PPARγ by the specific agonist GW1929. First, effective knockdown of caveolin-1 by small-interfering RNA (siRNA) markedly abolished the upregulation of GW1929 on PPARγ expression at both mRNA and protein levels; Then, in HEK293T, which has previously been reported with low endogenous caveolin-1 expression, exogenous expression of caveolin-1 significantly enhanced the upregulation of GW1929 on PPARγ expression compared with nontransfection control. In addition, inhibition of PPARγ by either siRNA or pharmacological inhibitor T0070907 led to increased phosphorylation of cellular mitogen-activated protein kinases ERK1/2 and p38. In parallel, GW1929 dramatically decreased the expression of the proliferative regulators (cyclin D1 and PCNA), whereas it increased the apoptotic factors (p21, p53, and mdm2) in hypoxic PASMCs. Furthermore, these effects of GW1929 could be partially reversed by recovery of the drug treatment. In combination, PPARγ activation by GW1929 reversibly drove the cell toward an antiproliferative and proapoptotic phenotype in a caveolin-1-dependent and -targeted mechanism.

Store‑operated calcium entry (SOCE) is critical for regulating the proliferation and metastasis of various cancer types. The present study aimed to investigate the role of SOCE on nicotine‑promoted proliferation of non‑small cell lung cancer (NSCLC) A549 cells. Cell proliferation was evaluated by BrdU incorporation assay. The SOCE and basal [Ca2+]i in NSCLC A549 cells were determined using Fura‑2 fluorescence microscopy. The mRNA and protein expression levels were determined by real‑time quantitative PCR and western blotting, respectively. The results demonstrated that, in A549 cells, the detectable store‑operated calcium channel (SOCC) components were TRPC proteins 1, 3, 4 and 6 and Orail, among which TRPC1, TRPC6 and Orai1 are expressed at relatively high levels with TRPC3 and TRPC4 at relatively low levels. Nicotine upregulated the mRNA and protein expression of TRPC1, TRPC6 and Orai1, increased basal [Ca2+]i and enhanced SOCE. Promotion of cell proliferation but not migration was observed in the nicotine‑treated cells, which was inhibited by SOCE inhibitor SKF‑96365. Furthermore, nicotine upregulated HIF‑1α expression in the A549 and NCI‑H292 cells. Silencing of HIF‑1α abrogated the increases in TRPCs and Orail and reversed the increases in basal [Ca2+]i and SOCE. Meanwhile, suppression of proliferation was observed in cells following HIF‑1α silencing. In conclusion, the results indicate that nicotine promotes lung cancer cell proliferation likely by upregulating HIF‑1α and SOCC components and therefore enhancing SOCE and increasing basal [Ca2+]i.

Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-β superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-α. BMP4 mutant (BMP4(+/-) ) mice presented with more severe lung inflammation in response to LPS or Pseudomonas aeruginosa, and lower bacterial load compared with that in BMP4(+/+) mice. Knockdown of BMP4 by siRNA increased LPS and TNF-α-induced IL-8 expression in 16HBE human airway epithelial cells and in primary human bronchial epithelial cells. Similarly, peritoneal macrophages from BMP4(+/-) mice produced greater levels of TNF-α and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4(+/+) mice. Administration of exogenous BMP4 attenuated the upregulation of TNF-α, IL-8, or KC induced by LPS and/or TNF-α in airway epithelial cells, and peritoneal macrophages. Finally, partial deficiency of BMP4 in BMP4(+/-) mice protected the animals from restrictive lung function reduction upon chronic LPS exposure. These results indicate that BMP4 plays an important anti-inflammatory role, controlling the strength and facilitating the resolution of acute lung inflammation; yet, BMP4 also contributes to lung function impairment during chronic lung inflammation.

The high tendency bio-oil towards polymerisation on heating makes bio-oil a potential feedstock for production of carbon materials. In this study, the cross-polymerisation of the typical furans and aromatic compounds in bio-oil was conducted to understand the impacts of structures of the aromatic compounds on their tendencies towards polymerisation. The results showed that the cross-polymerisation between furfural and the phenolics did exist. The reactivity of the aromatic compounds towards cross-polymerisation with furfural depended on the electron density of their benzene ring. Guaiacol and eugenol with the electron-donating functionalities were very reactive towards polymerisation, while toluene was not that reactive. The relatively electron-deficient benzene ring made benzoic acid almost inert in the polymerisation. Acetic acid showed insignificant effects on promoting the polymerisation, due to the weak acidity, while H2SO4 could remarkably promote the cross-polymerisation. Besides, the hydrophilicity/hydrophobicity of substituents on benzene rings affected the morphology and structure of polymers.

This study investigated the gasification of wood, weed, plastic, tire, carton and their mixtures using zeolite (A4 type) as a catalyst, with the purpose of investigating the potential interactions of the various feedstocks during gasification. The co-gasification of the mixed feedstock led to the occurrences of the cross-interactions, which substantially impacted the distribution of the products in gasification. During the co-gasification, the pyrolysis/gasification of the different feedstocks produced the reaction intermediates with varied structures that interacted with each other and with the char formed from the different feedstock. The interaction could promote the gasification of the tarry compounds into gaseous products, which could also promote the gasification of the char to lower the char yields. Further to this, the cross-polymerisation or cracking of the varied reaction intermediates also took place during the co-gasification, leading to the formation of more coke deposits on catalyst. The co-gasification of the mixed feedstocks significantly impacted the reaction network, impacting the formation of gases, tar, char and the coke on catalysts, originating from the cross-interaction among the reaction intermediates derived from the pyrolysis/gasification of the various feedstocks.

The anti-inflammatory function of tanshinone IIA (TIIA), an active natural compound from Chinese herbal medicine Danshen, has been well recognized, and therefore TIIA has been widely used to treat various inflammatory conditions associated with cardiac and lung diseases. Mucin 1 (Muc1) plays important anti-inflammatory roles in resolution of acute lung inflammation. In this study, we investigated the effects of TIIA on LPS-induced acute lung inflammation, as well as its relationship to Muc1 expression in mouse lung and MUC1 in human alveolar epithelial cells. TIIA pretreatment significantly inhibited LPS-induced pulmonary inflammation in both Muc1 wild-type ( Muc1+/+) and knockout ( Muc1−/−) mice, as manifested by reduced neutrophil infiltration and reduced TNF-α and keratinocyte chemoattractant levels in bronchoalveolar lavage fluid. The inhibitory effects of TIIA on airway inflammation were associated with reduced expression of Muc1 in Muc1+/+ mouse lung. Moreover, pretreatment with TIIA significantly inhibited LPS-induced MUC1 expression and TNF-α release in A549 alveolar epithelial cells. TNF-α upregulated MUC1 mRNA and protein expression in A549 cells, which was inhibited by pretreatment with TIIA. The LPS-induced MUC1 expression was blocked when A549 cells were transfected with siRNA targeting for TNF-α receptor 1. Furthermore, TIIA inhibited LPS-induced nuclear translocation of NF-κB and upregulation of Toll-like receptor 4 in A549 cells. Taken together, these results demonstrate that TIIA suppressed LPS-induced acute lung inflammation regardless of the presence of Muc1, and TIIA inhibited LPS- and TNF-α-induced MUC1/Muc1 expression in airway epithelial cells, suggesting that MUC1/Muc1 does not account for the mechanisms of the anti-inflammatory effects of TIIA in the airway.