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Background: Pulmonary hypertension (PH) associated with congenital heart disease (CHD) is the most common type of PH in pediatric patients. The airway microbiome profile in CHD-PH patients remains rarely studied. Methods: A total of 158 children were recruited for collection of oropharyngeal swabs to sequence the 16S ribosomal RNA ( 16S rRNA) V3-V4 region of respiratory microbiome, to establish a correlation between these bacterial groups and echocardiography indicators in CHD-PH patients. Results: Bacterial α- and β-diversity of the airway microbiome indicated a significantly lower richness in the CHD-PH group and compositional differences associated with the specific taxa and their relative abundances in the upper respiratory tract. Principal coordinate analysis showed that the pharynx microbiota composition in the CHD-PH group varied from that in the CHD or control group. The linear discriminant analysis effect size also highlighted an increased presence of Streptococcus and Rothia in pediatric CHD-PH patients. Comparison of microbial composition between pediatric and adult PH patients showed significant differences and separation of microbiota. The correlation between bacterial abundance and transthoracic echocardiography indexes in CHD-associated PH indicated that different groups of microbiomes may be related to different PH grades. Conclusions: In summary, our study reported the systematic definition and divergent profile of the upper respiratory tract microbiota in pediatric PH patients, CHD and reference subjects, as well as between pediatric and adult PH patients.

Piezo1 is an important mechanosensitive channel implicated in vascular remodeling. However, the role of Piezo1 in different types of vascular cells during the development of pulmonary hypertension (PH) induced by high shear stress is largely unknown.We used a rat PH model established by left pulmonary artery ligation (LPAL, for 2-5 weeks), which mimics the high flow and hemodynamic stress, to study Piezo1 contribution to pulmonary vascular remodeling.Right ventricular systolic pressure (RVSP), a surrogate measure for pulmonary arterial systolic pressure, and right ventricular wall thickness, a measure for right ventricular hypertrophy, were significantly increased in LPAL rats compared with Sham-control (SHAM) rats. Rats in LPAL-5w groups developed remarkable pulmonary vascular remodeling, while phenylephrine-induced contraction and acetylcholine-induced relaxation were both significantly inhibited in these rats. Upregulation of Piezo1, in association with increase in cytosolic Casup2+/supconcentration ([Casup2+/sup]subcyt/sub), was observed in pulmonary arterial smooth muscle cells (PASMCs) from LPAL-2w and LPAL-5w rats in comparison to the SHAM controls. Piezo1 upregulation in PASMCs from LPAL rats was directly related to Yes-associated protein (YAP)/ TEA domain transcription factor 4 (TEAD4). Piezo1 expression was also upregulated in the whole-lung tissue of LPAL rats. The endothelial upregulation of Piezo1 was related to transcriptional regulation by RELA (p65) and lung inflammation.The upregulation of Piezo1 in both PASMCs and ECs coordinates with each other via different cell signaling pathways to cause pulmonary vascular remodeling in LPAL-PH rats, providing novel insights into the cell-type specific pathogenic roles of Piezo1 in shear stress-associated experimental PH.

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.

Background and purpose Pulmonary veno-occlusive disease (PVOD) is a rare disease characterized by the obstruction of small pulmonary veins leading to pulmonary hypertension. However, the mechanisms underlying pulmonary vessel occlusion remain largely unclear. Experimental approach A mitomycin C (MMC)-induced PVOD rat model was used as in vivo animal model, and primarily cultured rat pulmonary microvascular endothelial cells (PMVECs) were used as in vitro cell model. Key results Our data suggested an endothelial-to-mesenchymal transition (EndoMT) may be present in the pulmonary microvessels isolated from either PVOD patients or MMC-induced PVOD rats. In comparison to the control vessels, vessels from both PVOD patients and PVOD rats had co-localized staining of specific endothelial marker von Willebrand factor (vWF) and mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the presence of cells that co-express endothelial and mesenchymal markers. In both the lung tissues of MMC-induced PVOD rats and MMC-treated rat PMVECs there were decreased levels of endothelial markers (e.g. VE-cadherin and CD31) and increased mesenchymal markers (e.g. vimentin, fibronectin and α-SMA) were detected indicating EndoMT. Moreover, MMC-induced activation of the TGFβ/Smad3/Snail axis, while blocking this pathway with either selective Smad3 inhibitor (SIS3) or small interfering RNA (siRNA) against Smad3, dramatically abolished the MMC-induced EndoMT. Notably, treatment with SIS3 remarkably prevented the pathogenesis of MMC-induced PVOD in rats. Conclusions and implications Our data indicated that targeted inhibition of Smad3 leads to a potential, novel strategy for PVOD therapy, likely by inhibiting the EndoMT in pulmonary microvasculature.

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.

Previous studies have suggested that dysbiosis of the gut microbiota is associated with the development of pulmonary hypertension (PH). In this study, we established a left pulmonary artery ligation (LPAL)-induced PH rat model due to high flow and hemodynamic stress and investigated the association between gut microbiota composition and host metabolome signatures (in both gut and lung tissues) by using multiomics and correlation analysis. The results showed that LPAL successfully induced PH, characterized by increased right ventricular systolic pressure, right ventricular hypertrophy and pulmonary vascular remodelling. Moreover, gut pathological abnormalities were observed in association with dramatic alterations in the gut microbiome and metabolome as well as the lung metabolome. The increased bacterial genus Sporobacter and decreased genera Eubacterium, Eubacteriaceae, Deltaproteobacteria and Desulfovibrio featured the altered gut microbiome in LPAL-PH versus SHAM rats. Moreover, imbalanced abundance of protective metabolites (e.g., butyrate, propionate) and pathogenic metabolites (e.g., proinflammatory mediators) were seen in the gut metabolome of LPAL-PH versus SHAM rats. In addition, the altered gut microbiome strongly correlated with the altered metabolome patterns in both the gut and lung of LPAL-PH rats. In conclusion, this study revealed significant gut dysbiosis in LPAL-PH rats, characterized by altered gut microbiota composition, in association with specific changes in gut and lung metabolome profiles. These findings enriched our understanding of the unique signature of the gut microbiome and the close association of the "gut-lung axis" in LPAL-PH induced by long-term high flow, leading to novel therapeutic, diagnostic or management paradigms for this subtype of PH.

What is the central question of this study? What is the role of breast cancer type 1 interacting protein C-terminal helicase 1 (BRIP1) polymorphism in chronic obstructive pulmonary disease (COPD)? What is the main finding and its importance? Variant rs10744996CA of BRIP1 increases the susceptibility of the Mongolian population to COPD. The expression of BRIP1 was significantly reduced in cigarette smoke extract-treated airway epithelial cells.Cigarette smoke is a major environmental pollutant that can induce DNA damage in humans. The development and progression of chronic obstructive pulmonary disease (COPD) are known to be related to the impairment of DNA repair. Breast cancer type 1 interacting protein C-terminal helicase 1 (BRIP1) plays an important role in DNA interstrand crosslink repair and double-strand break repair. However, the role of BRIP1 polymorphisms in COPD has not been previously described. In this study, whole genome sequencing was used to identify mutations, and single nucleotide polymorphism (SNP) genotyping was used to verify the selected SNPs. In addition the BRIP1 expression levels in 16HBE and A549 airway epithelial cells treated with or without cigarette smoke extract (CSE) were measured using western blotting and RT-qPCR. Rs10744996CA in the 3'-untranslated region (3'UTR) of BRIP1 was then genotyped in 1296 COPD cases and 988 healthy control subjects from a Mongolian population in northern China. Significant differences in the distribution of rs10744996CA variants between COPD and control groups (P = 0.001) were identified. Rs10744996CA was found to be associated with significantly increased COPD risk (adjusted odds ratio = 1.60, 95% CI = 1.30-1.98, P 0.0001). Additionally, rs10744996A genotype was found to interact with a family history of cancer and a history of x-ray exposure (P = 0.028 and 0.009, respectively). BRIP1 expression levels in 16HBE and A549 cells treated with CSE were significantly lower compared to the control treated cells. The rs10744996CA variant of BRIP1 increased the COPD susceptibility of the Mongolian population cohort. BRIP1 mRNA and protein expression levels were significantly reduced in conjunction with CSE-induced DNA damage in 16HBE and A549 cells.

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.

Recent studies have demonstrated the beneficial effects of STS in treating pulmonary hypertension by inhibiting the pulmonary vascular remodeling and suppressing the abnormally elevated proliferation and migration of PASMCs. However, the roles of STS on pulmonary vascular endothelium remain largely known.In this study, we investigated the effects and mechanisms of STS on pulmonary vascular endothelial dysfunction by using a chronic hypoxia-induced pulmonary hypertension (HPH) rat model, as well as in primarily cultured rat PMVECs and human ESC-ECs cell models.Firstly, a 21-day treatment of STS significantly prevents the disease development of HPH by normalizing the right ventricular systolic pressure and right ventricular hypertrophy, improving the cardiac output. Then, STS treatment markedly inhibits the hypoxia-induced medial wall thickening of the distal intrapulmonary arteries. Notably, STS significantly inhibits the hypoxia-induced apoptosis in both the pulmonary endothelium of HPH rats and primarily cultured PMVECs, through the stabilization of BMPR2 protein and protection of the diminished BMP9-BMPR2-Smad1/5/9 signaling pathway. In mechanism, STS treatment retrieves the hypoxic downregulation of BMPR2 by stabilizing the BMPR2 protein, inhibiting the BMPR2 protein degradation via lysosome system, and promoting the plasma membrane localization of BMPR2, all of which together reinforcing the BMP9-induced signaling transduction in both PMVECs and human ESC-ECs. However, these effects are absent in hESC-ECs expressing heterozygous dysfunctional BMPR2 protein (BMPR2STS may exert anti-apoptotic roles, at least partially, via induction of the BMP9-BMPR2-Smad1/5/9 signaling transduction in pulmonary endothelium and PMVECs.

BACKGROUND AND PURPOSE Recent studies reported therapeutic effects of monotherapy with either tumour suppressor p53 (p53) agonist or hypoxia-inducible factor 2α (HIF-2α) antagonist for pulmonary hypertension (PH). This study investigated whether a combined treatment of p53 agonist, Nutlin3a, and HIF-2α antagonist, PT2385, would be more effective than monotherapy, based on the cell type-divergent regulation of p53 in pulmonary arterial smooth muscle cells (PASMC) and endothelial cells (PAEC) in patients and animals with PH. EXPERIMENTAL APPROACH The SU5416/hypoxia-induced PH (SuHx-PH) rat model was used, along with cultured human PASMC and PAEC. Western blot, RT-PCR, siRNA and immunohistochemical methods were used along with echocardiography and studies with isolated pulmonary arteries. KEY RESULTS Hypoxia-induced proliferation of PASMC is associated with decreased p53, whereas hypoxia-induced PAEC apoptosis is associated with increased p53, via a HIF-2α-dependent mechanism. Combined treatment with Nutlin3a and PT2385 is more effective by simultaneously inhibiting the hypoxia-induced PASMC proliferation and PAEC apoptosis, overcoming the side-effects of monotherapy. These are (i) Nutlin3a exacerbates hypoxia-induced PAEC apoptosis by inducing p53 in PAEC and (ii) PT2385 inhibits PAEC apoptosis because HIF-2α is predominantly expressed in PAEC but lacks direct effects on the hypoxia-induced PASMC proliferation. In rats, combination treatment is more effective than monotherapy in reversing established SuHx-PH, especially in protecting pulmonary arterial vasculature, by normalizing smooth muscle thickening, protecting against endothelial damage and improving function. CONCLUSION AND IMPLICATIONS Combination treatment confers greater therapeutic efficacy against PH through a selective modulation of p53 and HIF-2α in PASMC and PAEC.

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.

The tumor-suppressive role of p53, a transcription factor that regulates the expression of many genes, has been linked to cell cycle arrest, apoptosis, and senescence. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular disease. We previously reported that rapid nuclear accumulation of hypoxia-inducible factor (HIF)-1α in pulmonary arterial smooth muscle cells (PASMCs) upregulates transient receptor potential channels and enhances Ca2+entry to increase cytosolic Ca2+concentration ([Ca2+]cyt). Also, we observed differences in HIF-1α/2α expression in PASMCs and pulmonary arterial endothelial cells (PAECs). Here we report that p53 is increased in PAECs, but decreased in PASMCs, isolated from mice with hypoxia-induced pulmonary hypertension (PH) and rats with monocrotaline (MCT)-induced PH (MCT-PH). The increased p53 in PAECs from rats with MCT-PH is associated with an increased ratio of Bax/Bcl-2, while the decreased p53 in PASMCs is associated with an increased HIF-1α. Furthermore, p53 is downregulated in PASMCs isolated from patients with idiopathic pulmonary arterial hypertension compared with PASMCs from normal subjects. Overexpression of p53 in normal PASMCs inhibits store-operated Ca2+entry (SOCE) induced by passive depletion of intracellularly stored Ca2+in the sarcoplasmic reticulum, while downregulation of p53 enhances SOCE. These data indicate that differentially regulated expression of p53 and HIF-1α/2α in PASMCs and PAECs and the cross talk between p53 and HIF-1α/2α in PASMCs and PAECs may play an important role in the development of PH via, at least in part, induction of PAEC apoptosis and PASMC proliferation.

Alteration in microbiota composition of respiratory tract has been reported in the progression of many chronic lung diseases, yet, the correlation and causal link between respiratory tract microbiota and the disease development of pulmonary hypertension (PH) remain largely unknown. This study aims to define and compare the respiratory microbiota composition in pharyngeal swab samples between patients with PH and reference subjects. A total of 118 patients with PH and 79 reference subjects were recruited, and the pharyngeal swab samples were collected to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of respiratory microbiome. The relative abundances in patients with PH were profoundly different from reference subjects. The Ace and Sobs indexes indicated that the microbiota richness of pharynx value is significantly higher; while the community diversity value is markedly lower in patients with PH, comparing to those of the reference subjects. The microbiota on pharynx showed a different profile between the 2 groups by principal component analysis. The linear discriminant analysis effect size also revealed a significantly higher proportion of Streptococcus , Lautropia , and Ralstonia in patients with PH than reference subjects. The linear discriminant analysis effect size output, which represents the microbial gene functions, suggest genes related to bacterial invasion of epithelial cells, bacterial toxins were enhanced, while genes related to energy metabolism, protein digestion and absorption, and cell division pathways were attenuated in patients with PH versus reference subjects. In summary, our study reports the first systematic definition and divergent profile of the upper respiratory tract microbiota between patients with PH and reference subjects.

Misbalanced bacterial ecosystem is likely involved in the pathogenesis of pulmonary hypertension (PH). Recent studies showed changes in the gut microbiota composition were associated with PH. To investigate whether the risk of PH causally resulted from gut microbiota alteration, we conducted a two-sample Mendelian randomization study. We identified quantitative trait locus as instrumental variables from genome-wide association study summary data. Microbial taxa affected by host genetic variation was proxied by 40 single nucleotide polymorphisms (SNPs) from 1812 European individuals, while microbial function was proxied by 16 SNPs from 984 European individuals. We derived SNPs-PH effect estimates from 463010 individuals in the UK Biobank. This study showed changes in microbial taxa and function units associated with host-microbe intersection (MetaCyc pathways and Gene Ontology terms with at least 2000 genes (GO2000 terms)) had no causal effect to develop PH, except decreased function units (Table 1). Further subgroup analysis indicated a decreased risk of secondary PH resulted causally from microbial function units per Z-score decrease (OR 0.999, 95% CI: 99998-0.99999, P=1.88×10−2). Our study supported a causal role of declining gut microbiota function in the etiology of PH. Suggestive evidence showed that host-microbe intersection, notably MetaCyc pathway components and GO2000 terms were associated with secondary PH.

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.

Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.

Background: Mucin 1 (MUC1) is a membrane tethered protein on airway epithelial cells. This protein is upregulated and plays an important anti-inflammatory role during acute lung inflammation. However, the relationship between sputum MUC1 level and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unknown. Methods: The levels of MUC1, IL-8, and TNF-α in induced sputum from 78 COPD patients were assessed by ELISA. The association between COPD exacerbation and MUC1 fragment levels was analyzed. An acute airway inflammation mouse model was established by intranasal LPS inhalation. The expression of Muc1 in lung and the levels of Muc1, TNF-α and KC in BAL fluid from mice were determined with western blotting and ELISA, respectively. Results: Higher levels of MUC1 membrane-tethered (CT) and extracellular (EC) fragments, cytokines TNF-α and IL-8, more leucocyte and neutrophil counts were found in sputum from COPD patients in acute than in remission phase. Linear regression analysis confirmed that the level of sputum MUC1 CT fragment is positively correlated with sputum neutrophil number and patients’ age; whereas the sputum EC fragment level is correlated inversely with FEV1/FVC value and positively with patients’ age. Inhalation of lipopolysaccharide (LPS) induced acute lung inflammation in mice which exhibited increased levels of Muc1 CT fragment in lung and only Muc1 EC fragment increase in BAL fluid. Conclusions: Unlike pure bacterial induced lung inflammation, both sputum MUC1 CT and EC fragments are increased during acute exacerbation of COPD. The clinical benefits from measuring the changes of various sputum MUC1 fragments in AECOPD need to be elucidated in future studies.

Skeletal muscle atrophy and dysfunction are common complications in the chronic obstructive pulmonary disease (COPD). However, the underlying molecular mechanism remains elusive. Serum response factor (SRF) is a transcription factor which is critical in myocyte differentiation and growth. In this study, we established a mouse COPD model induced by cigarette smoking (CS) exposure for 24 weeks, with apparent pathophysiological changes, including increased airway resistance, enlarged alveoli, and skeletal muscle atrophy. Levels of upstream regulators of SRF, striated muscle activator of Rho signaling (STARS), and ras homolog gene family, member A (RhoA) were decreased in quadriceps muscle of COPD mice. Meanwhile, the nucleic location of SRF was diminished along with its cytoplasmic accumulation. There was a downregulation of the target muscle-specific gene, Igf1. These results suggest that the CS is one of the major causes for COPD pathogenesis, which induces the COPD-associated skeletal muscle atrophy which is closely related to decreasing SRF nucleic translocation, consequently downregulating the SRF target genes involved in muscle growth and nutrition. The STARS/RhoA signaling pathway might contribute to this course by impacting SRF subcellular distribution.

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.

Backgrounds Bone morphogenetic protein receptor type 2 (BMPR2) signaling is anti-inflammatory. Decreased BMPR2 expression was seen in lung tissue from chronic obstructive pulmonary disease (COPD) patients. Methods The selected single nucleotide polymorphisms (SNPs) in BMPR2 were genotyped with polymerase chain reaction (PCR) ligase detection reaction. The effects of SNPs on gene expression were analyzed with luciferase assays. The mRNA and protein expression levels of BMPR2 in peripheral blood mononuclear cells (PBMCs) from COPD patients were determined by quantitative PCR and western blotting, respectively. Findings Two SNPs, rs6435156C > T and rs1048829G > T in the 3′-untranslated region (3′UTR) of BMPR2 were selected and genotyped in COPD case and healthy control subjects from southern Chinese population. Both of them were found associated with significantly increased COPD risk (adjusted odds ratio [OR] = 1.58 with 95% confidence interval [CI] = 1.14–2.15, P = 0.0056 for rs6435156C > T; adjusted OR = 1.47 and 95% CI = 1.10–1.97, P = 0.0092 for rs1048829G > T). Older age, cigarette smoking, family history of cancer and COPD were all factors that interacted with rs6435156C > T and rs1048829G > T causing increased COPD risk. Cigarette smokers with rs6435156 (CT + TT) or rs1048829 (GT + TT) were more susceptible to COPD than that with the rs6435156CC or rs1048829GG genotypes. In A549 human alveolar epithelial cells, luciferase reporter assays revealed that introduction of 3′UTR of BMPR2 plasmids carrying rs6435156T allele but not rs1048829T led to lower luciferase activity than the wild-type C or G alleles. Comparing to rs6435156CC, treatment with hsa-miR-20a mimics deceased whereas hsa-miR-20a inhibitor restored the luciferase reporter activity in cells transfected with constructs carrying rs6435156TT. BMPR2 mRNA and protein expressions were significantly lower in PBMCs from COPD smokers than that in non-smokers. COPD patients carrying rs6435156T allele had less BMPR2 expression in PBMCs. Interpretation This study demonstrated that both rs6435156C > T and rs1048829G > T variants in BMPR2 contributed to increased susceptibility to COPD. The T variants of rs6435156 increased COPD risk likely by binding with hsa-miR-20a, thus leading to downregulated BMPR2 expression in lung epithelial and immune cells., Highlights • The rs6435156 TT was associated with greater risk of COPD in smokers than in non-smokers. • Cigarette smokers with rs6435156 TT were more susceptible to COPD than those with CC genotype. • The T genotype of rs6435156 inhibited BMPR2 expression in PBMCs and lung epithelial cells. • The rs6435156 T is the functional binding site for miR-20a. COPD is characterized by abnormal inflammation and structural remodeling in the airway. Bone morphogenetic protein receptor type 2 (BMPR2) mediated signaling has been demonstrated to regulate pro-inflammatory responses in vasculature, and decreased expression of BMPR2 was found in COPD lungs; however the relationship of BMPR2 to COPD is unknown. We found that rs6435156 TT was the functional binding site for miR-20a in 3′UTR of BMPR2 and significantly increased risk of COPD in southern Chinese population; rs6435156C > T could modulate the susceptibility to COPD by interacting with cigarette smoking, which down-regulated BMPR2 expression dependent in hsa-miR-20a.

GIRD COPD Biobank is a multicenter observational study blood-based database with local characteristics, in order to investigate the causes, risk factors, pathogenesis, prevalence patterns and trends of COPD and promote new pathogenic insights in China.We enrolled 855 clinically COPD patients and 660 controls with normal lung function. Extensive data collection has been undertaken with questionnaires, clinical measurements, and collection and storage of blood specimens, following Standard Operating Procedures (SOP). All surveys had similar quality controls, supervisions, and training of the investigator team.Since September 2010, a total of 1515 subjects (1116 [73.7%] males; 855 [56.4%] diagnosed with COPD) were enrolled. Analyses of the design and interim results of the GIRD COPD Biobank Study identified patients with COPD were older, lower educational level, a longer history of pack-year smoking, less in kitchen fan usage, X-ray exposure, and history of disease (P0.01 for all); Most of the COPD subjects belonged to moderately severe or worse, stratified according to Global Lung Function Initiative (GLI); COPD patients had relatively more co-morbidities than controls; Environmental hazard exposures might be the main contributors to the reported respiratory symptoms; Cold air, haze, and influenza acted the top three factors to induce respiratory symptoms in both COPD cases and controls.The GIRD COPD Biobank Study has the potential to provide substantial novel insights into the genetics, biomarkers, environmental and lifestyle aspects of COPD. It is expected to provide new insights for pathogenesis and the long-term progression of COPD.

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.

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.