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The selective adenosine A2A receptor (A2AR) agonist regadenoson reduces inflammation due to lung ischemia-reperfusion injury (IRI). The objective of this study was to investigate molecular and cellular mechanisms by which regadenoson reduces IRI in lung transplant recipients. Fourteen human lung transplant recipients were infused for 12 hours with regadenoson and 7 more served as untreated controls. Plasma levels of high mobility group box 1 and its soluble receptor for advanced glycation end-products (sRAGE) were measured by Luminex. Matrix metalloproteinase (MMP) 2 and 9 were measured by gelatin zymography. Tissue inhibitor of metalloproteinase 1 was measured by mass spectroscopy. A2AR expression on leukocytes was analyzed by flow cytometry. MMP-9–mediated cleavage of RAGE was evaluated using cultured macrophages in vitro. Regadenoson treatment during lung transplantation significantly reduced levels of MMP-9 (P <.05), but not MMP-2, and elevated levels of tissue inhibitor of metalloproteinase 1 (P <.05), an endogenous selective inhibitor of MMP-9. Regadenoson infusion significantly reduced plasma levels of sRAGE (P <.05) during lung reperfusion compared with control subjects. A2AR expression was highest on invariant natural killer T cells and higher on monocytes than other circulating immune cells (P <.05). The shedding of RAGE from cultured monocytes/macrophages was increased by MMP-9 stimulation and reduced by an MMP inhibitor or by A2AR agonists, regadenoson or ATL146e. In vivo and in vitro studies suggest that A2AR activation reduces sRAGE in part by inhibiting MMP-9 production by monocytes/macrophages. These results suggest a novel molecular mechanism by which A2AR agonists reduce primary graft dysfunction. [ABSTRACT FROM AUTHOR]

• There is a threshold effect of biocrusts coverage on soil loss of grasslands. • The sediment from grasslands changes little when biocrust coverage is over 35%. • Biocrusts reduce sediment by directly covering and indirectly reducing erosion dynamics. Biocrusts (biological soil crusts) are ubiquitous living surface covers in dryland grasslands that play critical roles in erosion control. However, the performance of biocrusts in soil conservation in grasslands remains uncertain due to the limited knowledge of the linkage between biocrust coverage and soil loss. We established eight treatments, including bare soil, 30 % grass alone, and 30 % grass with biocrusts, with coverage ranging between 10 % and 60 %. The runoff rate, hydrodynamic parameters, and sediment yield rate were investigated via simulated rainfall experiments at an intensity of 90 mm h−1. We found that biocrusts significantly increased the soil surface roughness and Darcy–Weisbach resistance coefficient, leading to a decrease in flow velocity, Reynolds number, and Froude number in grasslands. Thus, biocrusts were found to significantly reduce runoff rate and sediment yield rate from grasslands compared to bare soil. Both the decrement of runoff rate (R) and sediment yield rate (S) were exponentially correlated with increasing biocrust coverage (R=0.981exp(−0.012x), R 2 = 0.639; S=13.515exp(−0.045x), R 2 = 0.889). There was a threshold coverage (35 %) for the impact of biocrusts on the sediment yield rate. Further analysis by the structural equation model (SEM) revealed that biocrusts influenced sediment yield through direct cover (path coefficient of −0.49) and indirectly by reducing runoff and velocity with path coefficients of −0.55 and −0.60, respectively. Results of this study break our preconceived notion that grasses are often thought to be the key to erosion control, when in fact biocrusts play an unignorable role in erosion control in grasslands. The study highlighted the importance of maintaining biocrusts to a threshold coverage in grasslands for soil erosion control. [ABSTRACT FROM AUTHOR]

Injectable intramyocardial biomaterials have promise to limit adverse ventricular remodeling through mechanical and biologic mechanisms. While some success has been observed by injecting materials to regenerate new tissue, optimal biomaterial stiffness to thicken and stiffen infarcted myocardium to limit adverse remodeling has not been determined. In this work, we present an in-vivo study of the impact of biomaterial stiffness over a wide range of stiffness moduli on ventricular mechanics. We utilized injectable methacrylated polyethylene glycol (PEG) hydrogels fabricated at 3 different mechanical moduli: 5 kPa (low), 25 kPa (medium/myocardium), and 250 kPa (high/supraphysiologic). We demonstrate that the supraphysiological high stiffness favorably alters post-infarct ventricular mechanics and prevents negative tissue remodeling. Lower stiffness materials do not alter mechanics and thus to be effective, must instead target biological reparative mechanisms. These results may influence rationale design criteria for biomaterials developed for infarct reinforcement therapy. Acellular biomaterials for cardiac application can provide benefit via mechanical and biological mechanisms post myocardial infarction. We study the role of biomaterial mechanical characteristics on ventricular mechanics in myocardial infarcts. Previous studies have not measured the influence of injected biomaterials on ventricular mechanics, and consequently rational design criteria is unknown. By utilizing an in-vivo assessment of ventricular mechanics, we demonstrate that low stiffness biomaterial do not alter pathologic ventricular mechanics. Thus, to be effective, low stiffness biomaterials must target biological reparative mechanisms. Physiologic and supra-physiologic biomaterials favorably alter post-infarct mechanics and prevents adverse ventricular remodeling. [Display omitted] [ABSTRACT FROM AUTHOR]

• Fragmented biocrusts intensify soil erosion. • The effect of biocrust fragmentation on sediment was greater than its effect on runoff. • Biocrust fragmentation increases sediment by reducing flow resistance. • A large patch size of biocrusts favors soil conservation. Biocrusts, which are a positive factor in soil conservation in drylands, are often distributed as a pattern of patches on the soil surface due to disturbances. The fragmentation of biocrusts patches increases with the intensity and frequency of disturbance, thereby reducing the ecological function of these patches. However, whether and how biocrust fragmentation affects runoff and sediment yield is unclear. Accordingly, we conducted a series of indoor simulated rainfall experiments by constructing 21 erosion pans (1 m × 0.7 m) with bare soil (control) and biocrust with a coverage of 60 % in different fragmentations under a rainfall intensity of 90 mm/h. The fragmentation of biocrust was characterized by patch density (PD) ranging from 1.43 to 31.43. Larger values of PD indicate greater intensity of fragmentation of the biocrust patches. The results showed that biocrust fragmentation significantly influences runoff and soil erosion. Compared to a biocrust PD of 1.43, a PD of 4.29–31.43 shortened the time to runoff by 16.7 %, increased the runoff rate by 0.4 %, and increased the sediment yield rate by 85.8 %. The runoff rate showed a nonlinear relationship with biocrust fragmentation, while the sediment yield rate decreased logarithmically (S = 6.987ln(x) + 18.985, R2 = 0.837). Biocrust fragmentation affected hydrological connectivity (Flowlength, FL) and the overland flow pattern and regime (R2 = 0.525–0.990). The largest FL increased from 95.10 to 110.43 cm as biocrust fragmentation increased, thus indicating increased hydrological connectivity. Generally, biocrust fragmentation indirectly affected sediment yield by reducing Darcy–Weisbach resistance and increasing FL, with path coefficients of −0.71 and 0.80, respectively. The results of our study partly revealed the effect and mechanisms of biocrust fragmentation on their soil conservation function. Such results provide a new perspective for assessing soil erosion on biocrust-covered slopes and provide guidance for revising soil erosion models to include the effectiveness of biocrusts. [ABSTRACT FROM AUTHOR]

Objective The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. Methods Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A 2B receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity. Results EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmH 2 O, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH 2 O, P = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration. Conclusions Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality. [ABSTRACT FROM AUTHOR]

Objective Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. Methods Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. Results Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H 2 O vs 15.0 ± 4.6 mL/cm H 2 O) and 4 hours (30.6 ± 1.3 mL/cm H 2 O vs 17.7 ± 5.9 mL/cm H 2 O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. Conclusions Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool. [ABSTRACT FROM AUTHOR]

Background Despite the critical need for donor lungs, logistic and geographic barriers hinder lung utilization. We hypothesized that lungs donated after circulatory death subjected to 6 hours of cold preservation after ex vivo lung perfusion (EVLP) would have similar outcomes after transplantation as lungs transplanted immediately after EVLP, and that both would perform superiorly compared with lungs transplanted immediately after procurement. Methods Donor porcine lungs were procured after circulatory death and 15 minutes of warm ischemia. Three groups (n = 5 per group) were randomized: immediate left lung transplantation (Immediate group), EVLP for 4 hours followed by transplantation (EVLP group), or EVLP for 4 hours followed by 6 hours of cold preservation followed by transplantation (EVLP+Cold group). Lungs were reperfused for 2 hours before obtaining pulmonary vein samples for partial pressure of oxygen/fraction of inspired oxygen ratio calculations, airway pressures for compliance measurements, and wet/dry weight ratios. Results The partial pressure of oxygen/fraction of inspired oxygen ratios in the EVLP and EVLP+Cold groups were significantly improved compared with those in the Immediate group (429.7 ± 51.8 and 436.7 ± 48.2 versus 117.4 ± 22.9 mm Hg, respectively). In addition, dynamic compliance was significantly improved in the EVLP and EVLP+Cold groups compared with immediate group (26.2 ± 4.2 and 27.9 ± 3.5 versus 11.1 ± 2.4 mL/cmH 2 O, respectively). There were no differences in oxygenation capacity or dynamic compliance between the EVLP and EVLP+Cold groups. Inflammatory cytokine levels were significantly lower in the EVLP and EVLP+Cold groups. Conclusions Lungs donated after circulatory death can be successfully transplanted as much as 6 hours after EVLP. Cold preservation of lungs after ex vivo assessment and rehabilitation may improve organ allocation, even to distant recipients, without compromising allograft function. [ABSTRACT FROM AUTHOR]

Background Ischemia-reperfusion injury (IRI) is a major source of morbidity and mortality after lung transplantation. We previously demonstrated a proinflammatory role of adenosine A 2B receptor (A 2B R) in lung IR injury. The current study tests the hypothesis that A 2B R antagonism is protective of ischemic lungs after in vivo reperfusion or ex vivo lung perfusion (EVLP). Methods Mice underwent lung IR with or without administration of ATL802, a selective A 2B R antagonist. A murine model of EVLP was also used to evaluate rehabilitation of donation after circulatory death (DCD) lungs. DCD lungs underwent ischemia, cold preservation, and EVLP with Steen solution with or without ATL802. A549 human type 2 alveolar epithelial cells were exposed to hypoxia-reoxygenation (HR) (3 hours/1 hour) with or without ATL802 treatment. Cytokines were measured in bronchoalveolar lavage (BAL) fluid and culture media by enzyme-linked immunoassay (ELISA). Results After IR, ATL802 treatment significantly improved lung function (increased pulmonary compliance and reduced airway resistance and pulmonary artery pressure) and significantly attenuated proinflammatory cytokine production, neutrophil infiltration, vascular permeability, and edema. ATL802 also significantly improved the function of DCD lungs after EVLP (increased compliance and reduced pulmonary artery pressure). After HR, A549 cells exhibited robust production of interleukin (IL)-8, a potent neutrophil chemokine, which was significantly attenuated by ATL802. Conclusions These results demonstrate that A 2B R antagonism attenuates lung IRI and augments reconditioning of DCD lungs by EVLP. The protective effects of ATL802 may involve targeting A 2B Rs on alveolar epithelial cells to prevent IL-8 production. A 2B R may be a novel therapeutic target for mitigating IRI to increase the success of lung transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Biological soil crusts (BSCs) are extensively developed and commonly regarded as a kind of vegetation in desertification areas around the world. The natural recovery process of BSCs after disturbance and their long-term impacts on the soil water conditions are important but not well understood. In order to provide more insights into this problem, we set up two treatments including BSCs (natural BSCs without disturbance) and disturbed BSCs (the top 30mm of surface soil, including the BSC layer, was severely disturbed and completely removed) in a semi-arid environment on the Loess Plateau of China. Over the succeeding years, the natural recovery process of BSCs was qualitatively described and the soil water content at 0–90cm depth of the two treatments was consecutively monitored. The results showed the following: (1) it is possible to recover natural moss-dominated BSCs after severe disturbance under natural conditions, and the recovery process to BSC full-coverage took approximately three years; (2) the BSC disturbance greatly decreased soil water content by up to 18% and the effects gradually weakened with time; (3) the BSC disturbance decreased surface soil water content (0–70cm) by up to 24% but increased deep soil water content (80–90cm) by up to 13%; and (4) the BSC disturbance decreased soil water storage at 0–90cm by 7.8mm, 4.4mm, 8.0mm, and 4.9mm in the second, third, fourth, and seventh years, respectively. We concluded that the BSC disturbance degraded soil water conditions in the three to four years following the disturbance. Therefore, the artificial destruction of natural moss-dominated BSCs in a semi-arid region on the Loess Plateau of China should not be recommended as a land management practice for the improvement of soil water conditions. [Copyright &y& Elsevier]

Background: Damage to airway epithelium is closely related to the development of bronchiolitis obliterans (BO) in pulmonary transplantation. Rapamycin protects against BO development in a murine model, but its use in patients undergoing lung transplantation is limited by its side effects. We hypothesized that short-course rapamycin dosing could be used to prevent airway epithelium loss and protect against BO development in a murine model. Methods: A total alloantigenic mismatch, murine, heterotopic tracheal transplant model of BO was used. Animals were treated with either rapamycin or dimethyl sulfoxide (controls) according to one of three treatment regimens: (1) days 1 through 14 after transplantation, (2) days 3 through 7 after transplantation, or (3) days 14 through 28 after transplantation. Epithelial loss was assessed by use of hematoxylin and eosin stains 14 and 28 days after transplantation. Tracheal luminal obliteration was assessed at 28 days. Results: Early rapamycin treatment was protective against epithelial loss 14 days after transplantation in comparison with control animals (p < 0.001). Rapamycin treatment from days 1 to 14 was more effective at epithelial preservation (p = 0.002) and reducing luminal obliteration (p < 0.001) at 28 days than was rapamycin treatment from days 3 to 7. Late rapamycin treatment (days 14 to 28) allowed for recovery of the previously denuded epithelium at 28 days (92.5% epithelial loss to 35.6%) and a reduction in BO (p < 0.001). Conclusions: Short-course rapamycin treatment protects against airway epithelium loss and subsequent development of BO in a murine model. Because of its immunosuppressive and antifibrotic effects, rapamycin may prove to be the ideal medication to prevent chronic rejection and BO in patients undergoing lung transplantation. [Copyright &y& Elsevier]

Background: Fibrocytes are integral in the development of fibroproliferative disease. The CXCL12/CXCR4 chemokine axis has been shown to play a central role in fibrocyte migration and the development of bronchiolitis obliterans (BO) after lung transplantation. Inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin has been shown to decrease expression of both CXCR4 and its receptor agonist CXCL12. Thus, we hypothesized that rapamycin treatment would decrease fibrocyte trafficking into tracheal allografts and prevent BO. Methods: A total alloantigenic mismatch murine heterotopic tracheal transplant (HTT) model of BO was used. Animals were either treated with rapamycin or dimethyl sulfoxide (DMSO) for 14 days after tracheal transplantation. Fibrocyte levels were assessed by flow cytometry, and allograft neutrophil, CD3+ T-cell, macrophage, and smooth muscle actin (SMA) levels were assessed by immunohistochemistry. Tracheal luminal obliteration was assessed on hematoxylin and eosin (H&E) stains. Results: Compared with DMSO-treated controls, rapamycin-treated mice showed a significant decrease in fibrocyte levels in tracheal allografts. Fibrocyte levels in recipient blood showed a similar pattern, although it was not statistically significant. Furthermore, animals treated with rapamycin showed a significant decrease in tracheal allograft luminal obliteration compared with controls. Based on immunohistochemical analyses, populations of α-SMA–positive (α-SMA+) cells, neutrophils, CD3+ T cells, and macrophages were all decreased in rapamycin-treated allografts versus DMSO controls. Conclusions: Rapamycin effectively reduces recruitment of fibrocytes into tracheal allografts and mitigates development of tracheal luminal fibrosis. Further studies are needed to determine the cellular and molecular mechanisms that mediate the protective effect of rapamycin against BO. [ABSTRACT FROM AUTHOR]

Background: Severe ischemia-reperfusion (IR) injury leads to primary graft dysfunction after lung transplantation. Adenosine receptors modulate inflammation after IR, and the adenosine A3 receptor (A3R) is expressed in lung tissue and inflammatory cells. This study tests the hypothesis that A3R agonism attenuates lung IR injury by a neutrophil-dependent mechanism. Methods: Wild-type and A3R knockout (A3R-/-) mice underwent 1-hour left lung ischemia followed by 2-hours reperfusion (IR). A selective A3R agonist, Cl-IB-MECA, was administered (100 μg/kg intravenously) 5 minutes prior to ischemia. Study groups included sham, IR, and IR+Cl-IB-MECA (n = 6/group). Lung injury was assessed by measuring lung function, pulmonary edema, histopathology, and proinflammatory cytokines, and myeloperoxidase levels in bronchoalveolar lavage fluid. Parallel in vitro experiments were performed to evaluate neutrophil chemotaxis, and neutrophil activation was measured after exposure to acute hypoxia and reoxygenation. Results: Treatment of wild-type mice with Cl-IB-MECA significantly improved lung function and decreased edema, cytokine expression, and neutrophil infiltration after IR. The Cl-IB-MECA had no effects in A3R-/- mice; Cl-IB-MECA significantly decreased activation of wild-type, but not A3R-/-, neutrophils after acute hypoxia and reoxygenation and inhibited chemotaxis of wild-type neutrophils. Conclusions: Exogenous activation of A3R by Cl-IB-MECA attenuates lung dysfunction, inflammation, and neutrophil infiltration after IR in wild-type but not A3R-/- mice. Results with isolated neutrophils suggest that the protective effects of Cl-IB-MECA are due, in part, to the prevention of neutrophil activation and chemotaxis. The use of A3R agonists may be a novel therapeutic strategy to prevent lung IR injury and primary graft dysfunction after transplantation. [ABSTRACT FROM AUTHOR]

Objectives: Fibrocytes are integral in the development of fibroproliferative disease after lung transplantation. Undifferentiated fibrocytes (CD45+anti-collagen 1+CXCR4+) preferentially traffic by way of the CXCR4/CXCL12 axis and differentiate into smooth muscle actin-producing (CD45+CXCR4+α-smooth muscle actin+) cells. We postulated that an antibody directed against CXCL12 would attenuate fibrocyte migration and fibro-obliteration of heterotopic tracheal transplant allografts. Methods: A total alloantigenic mismatch murine heterotopic tracheal transplant model of obliterative bronchiolitis was used. The mice were treated with either goat-anti-human CXCL12 F(ab′)2 or goat IgG F(ab′)2. Buffy coat, bone marrow, and trachea allografts were collected and analyzed using flow cytometry. Tracheal luminal obliteration was assessed using hematoxylin-eosin and Direct Red 80 collagen stain. Results: Compared with the controls, the anti-CXCL12–treated mice showed a significant decrease in tracheal allograft fibrocyte populations at 7 and 21 days after transplantation. Bone marrow and buffy coat aspirates showed the same trend at 7 days. In the anti-CXCL12–treated mice, there was a 35% decrease in luminal obliteration at 21 days (65% vs 100% obliterated; interquartile range, 38% vs 10%; P = .010) and decreased luminal collagen deposition at 21 and 28 days after transplantation (P = .042 and P = .012, respectively). Conclusions: Understanding the role of fibrocytes in airway fibrosis after lung transplantation could lead to a paradigm shift in treatment strategy. Anti-CXCL12 antibody afforded protection against infiltrating fibrocytes and reduced the deterioration of the tracheal allografts. Thus, the CXCR4/CXCL12 axis is a novel target for the treatment of fibro-obliteration after lung transplantation, and the quantification of fibrocyte populations could provide clinicians with a biomarker of fibrosis, allowing individualized drug therapy. [Copyright &y& Elsevier]

Background: Ex vivo lung perfusion (EVLP) is a novel technique than can be used to assess and potentially repair marginal lungs that may otherwise be rejected for transplantation. Adenosine has been shown to protect against pulmonary ischemia-reperfusion (IR) injury through its A2A receptor. We hypothesized that combining EVLP with adenosine A2A receptor agonist treatment would enhance lung functional quality and increase donor lung use. Methods: Eight bilateral pig lungs were harvested and flushed with cold Perfadex (Vitrolife, Englewood, CO). After 14 hours of storage at 4°C, EVLP was performed for 5 hours on 2 explanted lung groups: (1) control group lungs (n = 4) were perfused with Steen Solution (Vitrolife) and dimethyl sulfoxide and (2) treated group lungs (n = 4) received 10 μM CGS21680, a selective A2A receptor agonist, in a Steen solution–primed circuit. Lung histologic features, tissue cytokines, gas analysis, and pulmonary function were compared between groups. Results: Treated lungs demonstrated significantly less edema as reflected by wet-dry weight ratio (6.6 versus 5.2; p < 0.03) and confirmed by histologic examination. In addition, treated lung demonstrated significantly lower levels of interferon-γ (IFN- γ) (45.1 versus 88.5; p < 0.05). Other measured tissue cytokine levels (interleukin [IL]-1β, IL-6, and IL-8) were lower in the treatment group, but values failed to reach statistical significance. The oxygenation index was improved in the treated group (1.5 versus 2.3; p < 0.01) as was mean airway pressure (10.3 versus 13; p < 0.009). Conclusions: Combined use of adenosine A2A agonist and EVLP significantly attenuates the inflammatory response in acutely injured lungs after IR and enhances pulmonary function. This combination may improve donor lung quality and could increase the donor lung pool for transplantation. [ABSTRACT FROM AUTHOR]

Background: With the exception of surgery, the standard platinum-based chemotherapeutic agents are the preferred treatment for non-small cell lung cancer (NSCLC); however little improvement (5-year survival) has been made. Therefore it is highly desirable to develop innovative therapeutic agents for NSCLC treatment. Methods: Highly enantioselective synthetic methods were developed and a broad compound library was established. Cell toxicity, cell sensitivity, cell proliferation, cell invasion, and three-dimensional colony formation assays were used to assess the anticancer potential of these compounds in non–small-cell lung cancer (NSCLC) cell lines. Results: We found that the S-form of compound PL54 (PL54S, 5-20 μM) exhibited strong anticancer activity in 5 tested NSCLC cell lines. We further synthesized a highly pure R-form enantiomer of PL54 (PL54R) and its racemate (PL54Rac) and characterized their anticancer activities. The results showed that PL54S is more potent than PL54R and PL54Rac against the tested cell lines. Furthermore, less cellular toxicity was observed in the normal human lung fibroblasts. Similarly, PL54S displayed greater anti–colony formation activity compared with PL54R and PL54Rac. The cellular sensitivity assay revealed that PL54S and PL54Rac significantly suppressed cologenic formation compared with PL54R and dimethyl sulfoxide controls (p < 0.01). All PL54 compounds (5 to 20 μM) significantly inhibited cell proliferation and invasion of the A549 cell line (p < 0.01). A soft agar colony formation assay revealed that PL54S and PL54Rac (10 mM), but not PL54R, significantly inhibited colony formation of tested NSCLC cells (p < 0.01). Conclusions: The stereospecific compounds may prove to be a novel technique for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Adenosine is produced in response to ischemia or inflammation and protects tissues from injury. Four adenosine receptors are critical in the physiologic negative-feedback mechanism for limitation and termination of tissue-specific and systemic inflammatory responses. Accumulating evidence has focused on the anti-inflammatory and immunosuppressive role of the adenosine 2A receptor (A2AR), and we have previously reported on its role in the development of bronchiolitis obliterans (BO) after lung transplantation. Few studies, however, have reported the role of the adenosine 2B receptor (A2BR) in BO. Data suggests that the A2BR has pro-inflammatory and pro-fibrotic roles. We hypothesized that adenosine signaling through A2BR is involved in the development of BO. Methods: A murine heterotopic tracheal model across a total alloantigenic mismatch was used to study A2BR signaling in BO. Tracheal transplants consisted of Balb/c donor tracheas transplanted into wild-type or A2BR knockout (KO) C57BL/6 recipients. Transplanted tracheas were removed 3, 7, 12, and 21 days after transplantation. The luminal obliteration was evaluated through hematoxylin and eosin staining, and the cellular infiltration (macrophage, neutrophil, CD3+ and Foxp3+ regulatory T cell) was detected by immunohistochemical staining. Results: Compared with allografts in wild-type recipients, tracheas transplanted into A2BR KO mice displayed less BO development on Day 21. A2BR KO mice had an increase in CD3+ T cells and CD4+/CD25+/Foxp3+ regulatory T cells than did wild-type mice on Day 7. By Day 12, more CD3+ T cells were present in the wild-type trachea compared with the A2BR KO, but the percentage of CD4+/CD25+/Foxp3+ regulatory T cells remained higher in the tracheas of A2BR KO mice. Conclusions: A2BR stimulation may promote the development of BO by inhibiting CD4+/CD25+/Foxp3+ regulatory T-cell infiltration. [Copyright &y& Elsevier]

Objective: Adenosine A2A receptor activation potently attenuates lung ischemia–reperfusion injury. This study tests the hypothesis that adenosine A2A receptor activation attenuates ischemia–reperfusion injury by inhibiting CD4+ T cell activation and subsequent neutrophil infiltration. Methods: An in vivo model of lung ischemia–reperfusion injury was used. C57BL/6 mice were assigned to either sham group (left thoracotomy) or 7 study groups that underwent ischemia–reperfusion (1 hour of left hilar occlusion plus 2 hours of reperfusion). ATL313, a selective adenosine A2A receptor agonist, was administered 5 minutes before reperfusion with or without antibody depletion of neutrophils or CD4+ T cells. After reperfusion, the following was measured: pulmonary function using an isolated, buffer-perfused lung system, T cell infiltration by immunohistochemistry, myeloperoxidase and proinflammatory cytokine/chemokine levels in bronchoalveolar lavage fluid, lung wet/dry weight, and microvascular permeability. Results: ATL313 significantly improved pulmonary function and reduced edema and microvascular permeability after ischemia–reperfusion compared with control. Immunohistochemistry and myeloperoxidase content demonstrated significantly reduced infiltration of neutrophils and CD4+ T cells after ischemia–reperfusion in ATL313-treated mice. Although CD4+ T cell–depleted and neutrophil-depleted mice displayed significantly reduced lung injury, no additional protection occurred when ATL313 was administered to these mice. Expression of tumor necrosis factor-α, interleukin 17, KC, monocyte chemotactic protein-1, macrophage inflammatory protein-1, and RANTES were significantly reduced in neutrophil- and CD4+ T cell–depleted mice and reduced further by ATL313 only in neutrophil-depleted mice. Conclusions: These results demonstrate that CD4+ T cells play a key role in mediating lung inflammation after ischemia–reperfusion. ATL313 likely exerts its protective effect largely through activation of adenosine A2A receptors on CD4+ T cells and neutrophils. [Copyright &y& Elsevier]

Background: Binding of adenosine to the anti-inflammatory Gs-coupled adenosine 2A receptor (A2AR) inhibits the activity of most inflammatory cells. Extensive preclinical evidence exists for the use of A2AR agonists in the prevention of acute ischemia-reperfusion injury. Activation of A2ARs on lymphocytes and antigen-presenting cells also attenuates the alloimmune response. Because ischemia-reperfusion injury and alloimmunity are risk factors for the development of bronchiolitis obliterans (BO), the objective of this study was to determine the effect of A2AR signaling on tracheal rejection in a mouse model of BO. Methods: A non-revascularized heterotopic tracheal model across a total alloantigenic mismatch was used to study A2AR signaling in a mouse model of BO. Tracheal transplants were performed using Balb/c donors into wild-type or A2AR knockout C57BL/6 recipient mice. Another group of Balb/c transplants into C57BL/6 recipients were also treated with a selective A2AR agonist. Tracheas were assessed at 3, 7, 12, 21, and 28 days after transplantation by hematoxylin and eosin staining, immunohistochemical staining, and collagen staining. Results: Compared with allograft tracheas in wild-type recipients, allografts in A2AR knockout recipients had increased inflammation and more severe BO development. Recipient wild-type mice treated with a selective A2AR agonist were significantly protected from lymphocyte infiltration and luminal occlusion, but fibro-obliteration still developed by 28 days after transplantation. Conclusions: Endogenous adenosine signals through the A2AR to attenuate inflammatory and immune factors involved in BO development. Synthetic A2AR agonists may provide a novel treatment strategy to prevent BO. [Copyright &y& Elsevier]

Objective: Ischemia–reperfusion injury continues to plague the field of lung transplantation, resulting in suboptimal outcomes. In acute lung injury, processes such as ventilator-induced injury, sepsis, or acute respiratory distress syndrome, extravascular fibrin has been shown to promote lung dysfunction and the acute inflammatory response. This study investigates the role of the fibrinolytic cascade in lung ischemia–reperfusion injury and investigates the interplay between the fibrinolytic system and the inflammatory response. Methods: Mice lacking the plasminogen activator inhibitor-1 gene (PAI-1 knock out, PAI-1 KO; and thus increased lysis of endogenous fibrin) and wild-type mice underwent in situ left lung ischemia and reperfusion. Fibrin content in the lung was evaluated by immunoblotting. Reperfusion injury was assessed by histologic and physiologic parameters. Proinflammatory mediators were measured in bronchoalveolar lavage fluid and plasma using enzyme-linked immunosorbent assays. Results: Ischemia–reperfusion causes fibrin deposition in murine lungs. Less fibrin was seen in PAI-1 KO mice than in wild-type mice subjected to the same ischemia–reperfusion conditions. By histologic criteria, more evidence of ischemia–reperfusion injury was noted (thickening of the interstium, cellular infiltration in the alveoli) in the wild-type than in PAI-1 KO mice. Physiologic parameters also revealed more ischemia–reperfusion injury in the wild-type than in PAI-1 KO mice. Cytokine and chemokines were elevated more in the wild-type group than the PAI-1 KO group. Conclusions: Lung ischemia–reperfusion injury triggers fibrin deposition in the murine lungs and fibrin creates a proinflammatory environment. Preventing fibrin deposition may reduce ischemia–reperfusion injury and inflammation. This finding may lead to novel treatment strategies for ischemia–reperfusion. [Copyright &y& Elsevier]

In this paper, a method is proposed to calculate the lateral response of offshore monopiles in sand under aerodynamic and hydrodynamic loads. The ultimate soil resistance is assumed to be linear with depth, and the subgrade reaction modulus is assumed to be nonlinear with relative density. The mechanical modelling is examined in the context of the soil‒pile interaction relationship, and the deformation mode of the soil‒pile system is determined. Considering the aerodynamic and hydrodynamic loads, the mechanical relationships of the soil‒pile system are established. The validation of the computational results with existing numerical simulations and centrifuge tests confirms the effectiveness of the methodology in this study. • A method to calculate the lateral response of offshore monopiles under aerodynamic and hydrodynamic loads is proposed. • The mechanical model is examined based on the soil‒pile interaction relationship, and the deformation mode is determined. • Considering the aerodynamic and hydrodynamic loads, the mechanical relationships of the soil‒pile system are established. • An iterative calculation method to determine the threshold depth of the limit condition of the soil is presented. [ABSTRACT FROM AUTHOR]

Biological soil crusts (biocrusts) provide key ecosystem services in dryland ecosystems, especially soil fertility and surface stability. The relationships between soil fertility and microbial communities have been demonstrated with successional stages of biocrusts, however, the effects of soil stability on microbial communities are poorly understood. Thus, we investigated the changes in microbial communities, soil stability and fertility with biocrust succession and sampled soils with biocrusts with increasing moss coverage in a semiarid climate in the Loess Plateau of China. The phospholipid fatty acid (PLFA) method was used to determine the structural diversity of the microbial groups. The results showed that soil cohesion (which represented the soil stability) increased by 40%, and that the content of organic matter, total N and available N was 93%, 8% and 1.9 times greater in the later successional moss than in the early successional cyanobacteria. Consequently, the microbial diversity according to the Shannon and Simpson indices increased by 1.80% and 0.44%, respectively, and the microbial biomass was 3.1 times higher in the moss biocrusts than in the cyanobacteria biocrusts in biocrust layer, and the underlying 0–2 cm soil layer showed the similar changes of soil properties and microbial communities with biocrust layer. These findings are important for achieving a better understanding of the functions and services of biocrusts and provide a prediction for ecosystem processes in dryland ecosystems. • Soil microbial biomass increases as the increment of moss coverage. • Soil microbial diversity increases as the increment of moss coverage. • Improved soil stability and fertility with biocrust succession drives the developed microbial communities. [ABSTRACT FROM AUTHOR]

This study proposes a nonlinear analytical method to predict the response of combined loaded offshore rigid monopiles near sandy slopes. Considering the slope effect, the method discusses the ultimate soil resistance before and behind the pile separately. The method assumes that the subgrade reaction modulus varies nonlinearly with relative density but linearly with depth. The equilibrium equation for the pile-soil system is obtained from the balance of forces and moments. By analyzing four mechanical models of rigid monopiles under combined loading and selecting three of them as the basis, a failure mode determination method is provided. The accuracy of this method is verified by comparing with indoor model test, 3D FEA model test and centrifugal test. [ABSTRACT FROM AUTHOR]

Objective B lymphocytes are generally considered to be activators of the immune response; however, recent findings have shown that a subtype of B lymphocytes, regulatory B lymphocytes, play a role in attenuating the immune response. Bronchiolitis obliterans remains the major limitation to modern-day lung transplantation. The role of regulatory B lymphocytes in bronchiolitis obliterans has not been elucidated. We hypothesized that regulatory B lymphocytes play a role in the attenuation of bronchiolitis obliterans. Methods We performed a standard heterotopic tracheal transplant model. Tracheas from Balb/c mice were transplanted into C57BL/6 recipients. Rapamycin treatment and dimethyl sulfoxide control groups were each treated for the first 14 days after the transplant. Tracheas were collected on days 7, 14, and 28 post-transplantation. Luminal obliteration was evaluated by hematoxylin–eosin staining and Picrosirius red staining. Immune cell infiltration and characteristics, and secretion of interleukin-10 and transforming growth factor-β1 were accessed by immunohistochemistry. Cytokines and transforming growth factor-β1 were measured using the Luminex assay (Bio-Rad, Hercules, Calif). Results The results revealed that intraperitoneal injection of rapamycin for 14 days after tracheal transplantation significantly reduced luminal obliteration on day 28 when compared with the dimethyl sulfoxide control group (97.78% ± 3.63% vs 3.02% ± 2.14%, P < .001). Rapamycin treatment markedly induced regulatory B lymphocytes (B220 + IgM + IgG − IL-10 + TGF-β1 + ) cells when compared with dimethyl sulfoxide controls. Rapamycin treatment inhibited interleukin-1β, 6, 13, and 17 on days 7 and 14. Rapamycin also greatly increased interleukin-10 and transforming growth factor-β1 production in B cells and regulatory T lymphocytes infiltration on day 28. Conclusions Mammalian target of rapamycin inhibition decreases the development of bronchiolitis obliterans via inhibition of proinflammatory cytokines and increasing regulatory B lymphocytes cell infiltration, which subsequently produces anti-inflammatory cytokines and upregulates regulatory T lymphocyte cells. [ABSTRACT FROM AUTHOR]

Objectives: Loss of epithelial cells is one of the key factors that lead to airway fibrosis. Loss of epithelial cells may decrease the barrier to host cell infiltration into the lumen, allowing deposition of extracellular matrix, with subsequent obliteration of the airway. The objective of this study was to determine whether injection of epithelial cells/progenitor cells from the recipient into the lumen of the donor trachea could prevent bronchiolitis obliterans (BO) in a mouse heterotopic tracheal transplantation (HTT) model. Methods: A major histocompatibility complex class I and class II mismatch of mouse HTT model of BO was used. Epithelial cells from recipient mice were isolated and reinjected into the lumen of the allografts on day 3 after transplantation. Rag-1 knock-out and isografts were also performed as controls. The grafts were analyzed by immunohistochemistry and densitometric analysis. Results: The results demonstrated that tracheal epithelium was lost by day 3, regenerated between 3 to 7 days, and was lost again in all allografts, but not in the isografts or in Rag-1 knock-out groups by day 12. The reconstituted epithelium was donor originated on day 7 based on green fluorescent protein staining. Furthermore, with the injection of recipient cells into the tracheal lumen, loss of the epithelium was not observed and the luminal obliteration was significantly less in the allografts. Conclusions: Injection of recipient epithelial cells prevents the second phase of epithelial loss and significantly decreases BO development in an HTT model. Clinically, the use of injected recipient epithelial cells could be a novel treatment for BO. [ABSTRACT FROM AUTHOR]

Soil erosion and subsequent land degradation contributed to societal collapse in the past and are a leading cause of desertification in arid and semi-arid regions. Biological soil crusts (biocrusts) are ubiquitous living covers in many arid and semiarid ecosystems that have an important role in soil stabilization and erosion prevention. The “Grain for Green” ecological project improved vegetation recovery, and led to an extensive development of biocrusts across the Loess Plateau region in China, one of the most eroded regions in the world. The expansion of biocrusts was instrumental in reducing soil loss in a very large, severely eroded region of the Loess Plateau. We hypothesized that development of biocrusts would change soil organic matter (SOM) and soil particle size distribution (PSD), thereby reducing soil erodibility and soil loss. We sampled 56 sites that were passively revegetated grasslands on former croplands and 3 bare soil sites in the Loess Plateau region, and used the erosion productivity impact calculator (EPIC) model combined with simulated rainfall to test our assumption. The PSD and SOM content varied significantly among biocrust types and successional stages. The SOM content was 4 times higher in moss dominated biocrust and 1.5 times greater in cyanobacterially dominated biocrust than bare soil. More fine-particles (< 0.01 mm) and fewer coarse-particles (0.05–0.25 mm) were present in biocrusts than in bare soil. Modeled soil erodibility decreased significantly as biocrust biomass increased, mainly due to increase in SOM content, reducing the predicted soil loss by up to 90%. Finally, the prevalence of moss biocrust was a better predictor of soil erodibility than cyanobacteria in the Loess Plateau region. We conclude that biocrusts were a decisive factor for the initial reduction of soil erosion, which must be considered explicitly in models that aim to predict and manage soil loss on the Loess Plateau. [ABSTRACT FROM AUTHOR]

[Display omitted] • Under low-cover vegetation, biocrust was dominant in slowing the flow velocity. • Vegetation and biocrust interacted with each other to create additional resistance. • The biocrust had a larger flow resistance than both grass and shrub. • Form resistance of vegetation and biocrust played a vital role in total resistance. Biological crust (BSC) is a common kind of ground cover that affects overland flow together with vegetation. It is important to understand the hydrodynamic mechanism of slope covered by both vegetation and BSC to clarify the water erosion dynamics. However, the coupling effects of vegetation and BSC on overland flow characteristics are still unclear. In this study, simulated rainfall was employed to explore the effects of different combinations of grasses, shrubs and BSC on the hydrodynamic characteristics of flow. The results showed that grasses, shrubs, BSC and vegetation combinations significantly reduced the flow velocity. Compared with the control check (CK), the flow velocities of the more BSC (MBSC), grass cover (GC) and shrub cover (SC) treatments were reduced by 50 %, 32 % and 14 %, respectively. The detention coefficient of different treatments increased with increasing BSC coverage. This result indicated that BSC played a dominant role in slowing the flow velocity under low-cover vegetation. The Froude number (Fr) of CK, GC, SC, and SC+GC were > 1 during rainfall, indicating supercritical flow. The average Fr of the other treatments was < 1, but Fr > 1 was found in the less BSC (LBSC) and SC+LBSC treatments. The total flow resistance under different vegetation combinations did not conform to the simple linear stacking relationship. The interaction effect between different covers generated additional resistance, which varied among different ground cover combinations. The relationship between resistance coefficient (f) and Reynolds number (Re) gradually changed from a negative correlation for bare slopes to a positive correlation when vegetation or BSC existed, indicating that form resistance played a dominant role. It was concluded that BSC had a dominant effect on the hydraulic characteristics of overland flow in all ground cover treatments. This research provides a theoretical basis for the mechanism of erosion dynamics on slopes with combined vegetation and BSC. [ABSTRACT FROM AUTHOR]

Abstract: To assess the potential correlation between basal cell layer disruptions and leukocyte infiltration, consecutive sections of normal (n =5) and tumor (n =50) prostate tissues were double immunostained for cytokeratin 34βE12 (CK 34βE12) plus leukocyte common antigen, Ki-67, or proliferating cell nuclear antigen (PCNA). Of 2047 acini and ducts examined, 201 contained focal basal cell layer disruptions. Of those, 183 (91%) showed leukocyte infiltration, compared to 67 (33.3%) in 201 morphologically comparable structures with an intact basal cell layer (P &#60;0.01). Basal cell layers adjacent to or surrounded by leukocytes were often attenuated or fragmented, and leukocytes were generally located at or near disruptions. Disrupted basal cell layers showed a markedly reduced proliferation rate, compared to their non-disrupted counterparts. Cells overlying focal basal cell layer disruptions often displayed distinct changes in the size, nuclear shape, density, and polarity, compared to those away from disruptions. A vast majority of proliferating tumor cells were located at or near basal cell layer disruptions. These findings suggest that focal basal cell layer disruptions and leukocyte infiltration are correlated events, representing a potential trigger factor for prostate tumor invasion. [Copyright &y& Elsevier]

Currently, there are no clinically approved treatments for ischemia-reperfusion injury after lung transplantation. Pre-clinical animal models have demonstrated a promising efficacy of adenosine 2A receptor (A 2A R) agonists as a treatment option for reducing ischemia-reperfusion injury. The purpose of this human study, is to conduct a Phase I clinical trial for evaluating the safety of continuous infusion of an A 2A R agonist in lung transplant recipients. An adaptive, two-stage continual reassessment trial was designed to evaluate the safety of regadenoson (A 2A R agonist) in the setting of lung transplantation. Continuous infusion of regadenoson was administered to lung transplant recipients that was started at the time of skin incision. Adverse events and dose-limiting toxicities, as pre-determined by a study team and assessed by a clinical team and an independent safety monitor, were the primary end-points for safety in this trial. Between January 2018 and March 2019, 14 recipients were enrolled in the trial. Of these, 10 received the maximum infused dose of 1.44 µg/kg/min for 12 hours. No dose-limiting toxicities were observed. The steady-state plasma regadenoson levels sampled before the reperfusion of the first lung were 0.98 ± 0.46 ng/ml. There were no mortalities within 30 days. Regadenoson, an A 2A R agonist, can be safely infused in the setting of lung transplantation with no dose-limiting toxicities or drug-related mortality. Although not powered for the evaluation of secondary end-points, the results of this trial and the outcome of pre-clinical studies warrant further investigation with a Phase II randomized controlled trial. [ABSTRACT FROM AUTHOR]

Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs. A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion. After transplant, left lung–specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 ± 87.7 mm Hg vs. 252.7 ± 166.0 mm Hg, p = 0.017; 4-hour: 429.7 ± 93.6 mm Hg vs. 231.5 ± 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 ± 9.4 ml/cm H 2 O vs. 10.2 ± 3.5 ml/cm H 2 O, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 ± 0.7 vs. 8.8 ± 1.1, p = 0.040) and interleukin-1β expression (927 ± 300 pg/ng protein vs. 2,070 ± 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group. EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output. [ABSTRACT FROM AUTHOR]

The underground coal gasification (UCG) mining technology constitutes an innovative form of clean energy technology pertaining to coal resources. The sandstone specimens from the roof and floor of coal seam were collected and heat treated at 25 °C–800 °C in laboratory. According to the test results of physical parameters, 400 °C is the temperature turning point for the physical parameters such as mass, longitudinal P-wave velocity, porosity, and water absorption of sandstone specimens to change from "slow" to "drastic". The uniaxial compression test showed that the uniaxial compressive strength (UCS) of sandstone specimens decreases by 3.22% when the temperature rises from 25 °C to 200 °C, and by 5.70% when the temperature rises from 600 °C to 800 °C, both of which show temperature degradation effect. However, in the range of 200 °C–600 °C, the average UCS of sandstone specimens increases from 122.80 MPa to 162.54 MPa, showing obvious strength strengthening effect. In order to fully elucidate the mechanism of mechanical properties strengthening and degradation of tunnel surrounding rock under high temperature, X-ray diffraction (XRD), nuclear magnetic resonance (NMR), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were combined in the experiment. We concluded that these two intensity effects can be explained by physical and chemical reactions, including mineral composition thermal expansion, thermally induced microcrack and healing effects, phase transformation of the rock-forming mineral quartz, dehydration and thermal decomposition of mica, as well as dehydration and dehydroxylation of illite. The research results can provide theoretical basis for UCG roof and floor disaster prevention evaluation and tunnel support system design. • Rock performances evaluation of roof and floor for use in UCG applications. • The strength degradation and strengthening effects of high temperature sandstone have been discussed. • The physical and mechanical properties of sandstone are changed by temperature, and 400 °C is the threshold temperature. • The changes of physical mechanics of high temperature sandstone have been elucidated in macroscopic and microscopic aspects. • The thermal degradation and strengthening effects are caused by the physical and chemical reactions of rock-forming minerals. [ABSTRACT FROM AUTHOR]