•In-situ treatment of site soil using DJM technique and SPC binder is presented.•Solidified/stabilized soil exhibits satisfactory long-term performance after 326 days.•Leached concentrations of heavy ...metals and COD in soil are considerably reduced.•Soil resistance and acid neutralization capacity are remarkably improved.•In-situ field trial coincides well with lab study in strength/leaching properties.
In this study, in-situ treatment using dry jet mixing construction method and SPC (single superphosphate and calcium oxide) new binder are used to solidify/stabilize a heavy metal contaminated site soil with relatively high content of organic matters. Time-dependent field performance of the soils at 41 and 326 days after treatment is evaluated, which includes electrical conductivity (EC), leachability of heavy metals and chemical oxygen demand (COD), soil penetration resistance, acid neutralization capacity (ANC), and chemical speciation of heavy metals. The results indicate that the stabilized soils exhibit satisfactory performance which is comparable with the laboratory study. In-situ SPC treatment significantly decreases EC values and increases penetration resistance values of the soils. Leachability of lead, zinc, cadmium and COD decreases with increasing SPC content or curing time. Large percentages of heave metals in the soils are transformed from exchangeable fractions to residual fractions after treatment. These, coupled with the improved ANC, result in low heavy metal leachability in stabilized soils.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With 90% of global CO2 emissions being energy-related, promoting the transition to renewable energy is the first task of green development. The Asia-Pacific region accounts for more than half of the ...world's energy consumption, although progress on energy transition is still being made slowly. Thus, this research examines the effects of natural extreme events and green innovation on the sustainable goals for energy transition in 49 APAC economies between 2000 and 2019. The findings demonstrate that green innovation influences access to clean cooking (4.2%), encourages renewable energy consumption (3.9%), and lowers energy intensity (0.9%). While natural extreme events hamper progress on clean cooking access, they increase renewable energy consumption. By encouraging the modernization of industrial structures and renewable energy capacity, green innovation supports such an energy transition. The impact of green innovation differs significantly across economies, with non-OECD countries experiencing a greater influence than OECD countries.
•This research examines the effects of natural extreme events and green innovation on the sustainable goals.•For energy transition in 49 APAC economies between 2000 and 2019.•The findings demonstrate that green innovation most influences access to clean cooking.•While natural extreme events hamper progress on clean cooking access, they increase renewable energy consumption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association ...between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC).
In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation.
Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation ...resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage‐mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3‐associated phagocytosis (LAP), a non‐canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G‐protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL‐induced efferocytosis, anti‐colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3‐associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.
Synopsis
Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis.
COL has been identified as a novel efferocytosis enhancer that ameliorates mouse colitis.
COL binds to and biasedly activates FPR2, leading to enhanced efferocytosis in macrophages.
FPR2 emerges as a promising therapeutic target for the treatment of inflammatory diseases through modulating LC3‐associated efferocytosis in macrophages.
Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The H2O molecule dissociation on the alkali-earth (Ba and Mg) or transition-metal (Ti)-embedded nitrogen-doped graphene was studied systematically using first-principles calculation. The ...metal-embedded nitrogen-doped graphene (MN4-graphene) (M = Ba, Mg and Ti) membranes are good candidates for single-atom catalysts (SACs), because the single metal atom can be strongly trapped in the divacancy of the MN4-graphene membranes and exists in the isolated form. The significant activation of the reactant H2O molecule was observed. The binding energy of the first H atom of H2O molecule adsorbed on the MN4-graphene (M = Ba, Mg and Ti) membranes are 2.88 eV, 3.11 eV and 0.75 eV respectively, which are notable smaller than that 6.01 eV for free H2O molecule. Thus, the TiN4-graphene membrane can remarkably decrease the potential barrier of H atom dissociated from H2O molecule, which is a very promising SAC candidate for molecular dissociator. Our report comes as a first report towards the demonstration of the MN4-graphene membranes for the H2O molecule dissociation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A highly sensitive photoelectrochemical (PEC) biosensor without external bias was developed in this study. The biosensor was configured with a p-Cu2O and n-ZnO heterostructure. Hexamethylenetetramine ...(HMTA) and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) was used to improve the crystal structure of Cu2O and ZnO and reduce the defects in the Cu2O/ZnO interface. This fabrication method provided the highly crystallized Cu2O/ZnO structure with excellent electrical property and photoresponse in visible light. The structure was applied to a biosensor for detecting two different cancerous levels of esophageal cells, namely, OE21 and OE21-1, with a high gain in photocurrent (5.8 and 6.2 times, respectively) and a low detection limit (3000 cells in 50 μL). We believe that such a p-n heterojunction PEC biosensor could advance biosensor development and provide a promising candidate for biomedical applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Most tumor cells take up more glucose than normal cells. Splicing dysregulation is one of the molecular hallmarks of cancer. However, the role of splicing factor in glucose metabolism and tumor ...development remains poorly defined. Here, we show that upon glucose intake, the splicing factor SRSF5 is specifically induced through Tip60-mediated acetylation on K125, which antagonizes Smurf1-mediated ubiquitylation. SRSF5 promotes the alternative splicing of CCAR1 to produce CCAR1S proteins, which promote tumor growth by enhancing glucose consumption and acetyl-CoA production. Conversely, upon glucose starvation, SRSF5 is deacetylated by HDAC1, and ubiquitylated by Smurf1 on the same lysine, resulting in proteasomal degradation of SRSF5. The CCAR1L proteins accumulate to promote apoptosis. Importantly, SRSF5 is hyperacetylated and upregulated in human lung cancers, which correlates with increased CCAR1S expression and tumor progression. Thus, SRSF5 responds to high glucose to promote cancer development, and SRSF5-CCAR1 axis may be valuable targets for cancer therapeutics.
Background
Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further ...evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging.
Methods
A tumour necrosis factor (TNF)‐α‐induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)‐treated 8‐week‐old model mice and 23‐month‐old (aged) mice were used to examine the therapeutic effects of handelin on cachexia‐ and aging‐induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis.
Results
Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF‐α‐induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin‐like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin‐1 expression, inhibited nuclear factor‐κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS‐treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross‐sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti‐inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant‐related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL‐1β levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy.
Conclusions
Handelin ameliorated cachexia‐ and aging‐induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Employ panel data to study the influence of political ideology on innovation.•Test whether or not the changes in political ideology of a government influence innovation promotion.•A robustness test ...by choosing the re-elected and non-alternated governments.
This study investigates the relationship between government ideology and technical innovativeness of the whole country by using multinational panel data covering 110 countries from 1995 to 2015 and by employing comprehensive indicators for technical innovation, i.e. trademark and patent application in empirical research. We utilize the panel generalized method of moment (GMM) technique to introduce dynamic variables in order to avoid the bias caused by potential endogeneity. Next, we generate three cross items to examine whether the effect of government ideology on technical innovation differs under different circumstances. We then change the measurement of government ideology to assure the reliability of our empirical results, further investigate whether the changes of political ideology influence technical innovation, and carry out a robustness test by dividing the whole sample into two sub-samples based on the level of democracy, by employing two samples which limited by 3 main coalition parties in government at most, such as re-elected government and non-alternated government in countries. Overall, the empirical results show that a leftist ruling party inhibits the progress of technical innovation, whereas a right-wing ruling party promotes the appearance of new technology. The effect of government ideology on innovation is not similar under some circumstances. More evidence is presented by using two dummy variables to represent left-wing and right-wing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This research empirically analyzes the impact of various instruments of economic sanctions on official exchange rate volatility by employing data from a panel of 23 target countries covering the ...period 1996–2015 and using the Least Squares Dummy Variable Corrected (LSDVC) model. Our findings suggest that economic sanctions do significantly influence the target countries’ exchange rate volatility. Specifically, we are able to see different sanction present its different effects on exchange rate volatility. Furthermore, the robustness evidence of the eliminating country as Iran, eliminating variable of political ideology, intercepting time period, cross-sectional regression analysis, using real exchange rate volatility as proxy variable and a new sanctions database, are basically consistent with the previous finding. Overall, our empirical findings offer implications for those sanctioned countries about how to stabilize their exchange rate when facing sanctions.
•We investigate the relationship between economic sanctions and exchange rate volatility.•We use the panel data of 23 target countries from 1996 to 2015.•The method used in this article is the Least Squares Dummy Variable Corrected (LSDVC) model.•We find that the different ways, time and distance of sanctions will affect the effect of sanctions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP