Prognostic value of virtual portal pressure gradient response in compensated cirrhotic patients treated with carvedilol.

AIM: This study aimed to assess the prognostic significance of virtual portal pressure gradient (vPPG) response to carvedilol in patients with compensated cirrhosis (CC). METHODS: Compensated cirrhosis patients with high-risk varices were prospectively enrolled to receive carvedilol for prevention of first variceal hemorrhage (VH) and followed up for 1 year. The vPPG response was defined as a reduction of vPPG >10% from baseline after 1-month therapy. Logistic and Cox regression analyses were performed to identify independent predictors for vPPG response and first decompensation, respectively. Competitive risk models were constructed to predict disease progression, and validated using the C-index, Kaplan-Meier analysis, competitive risk analysis, and calibration curves. RESULTS: A total of 129 patients completed this study, of whom 56 (43.4%) achieved vPPG response and were referred as vPPG responders. Baseline vPPG, red color sign, Model for End-stage Liver Disease score, serum monocyte chemoattractant protein-1 (MCP-1), and laminin levels significantly correlated with vPPG response, which itself was further documented as an independent predictor of VH, ascites, and overall decompensation events in CC. Moreover, the red color sign or Child-Turcotte-Pugh score effectively predicted VH, while ascites correlated well with portal flow velocity or MCP-1. The predictive models for VH and ascites showed a good discrimination with C-index values of 0.747 and 0.689 respectively, and the high consistency on calibration curves. CONCLUSION: The vPPG response could be used as a noninvasive tool for prediction of disease progression in patients with CC.

HMGB1-induced autophagy facilitates hepatic stellate cells activation: a new pathway in liver fibrosis.

High-mobility group box-1 (HMGB1) plays a context-dependent role in autophagy, which is required for hepatic stellate cells (HSCs) activation. However, the significance of HMGB1-induced HSCs autophagy in liver fibrosis has not been elucidated. Here, we first documented an enrichment of peripheral and intrahepatic HMGB1 signal in hepatitis B virus (HBV)-related liver fibrosis progression, and presented a direct evidence of anatomic proximity of HMGB1 with a-SMA (a marker for HSCs activation) in cirrhotic liver specimens. Then, we demonstrated the autophagy-inducing effects by serum-sourced HMGB1 in both primary murine HSCs and human HSCs cell line (LX-2), reflected by increased number of autophagic vacuoles (AVs) under the transmission electron microscope (TEM) and up-regulated protein expression of lipidated microtubule-associated light chain 3 (LC3-II) (a marker for autophagosome) in Western blot analysis. Intriguingly, there is a possible translocation of endogenous HMGB1 from the nucleus to cytoplasm to extracellular space, during exogenous HMGB1-induced HSCs autophagy. Meanwhile, the dose- and time-dependent effects by recombinant HMGB1 (rHMGB1) in enhancing LX-2 autophagy and fibrogenesis have been revealed with activated extracellular regulated protein kinase (ERK)/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) and restrained mammalian target of rapamycin (mTOR)/STAT3 signaling pathways. Additionally, the ERK or JNK inhibitor could not only inhibit rHMGB1-induced autophagy and fibrogenesis in LX-2 cells, but also restore the suppressed mTOR and STAT3 pathways. Furthermore, using LC3-siRNA transfected LX-2, we found HMGB1-induced fibrogenesis is dependent on its autophagy-inducing effects. Finally, we elucidated the involvement of extracellular HMGB1-receptor for advenced glycation end product (RAGE) axis and endogenous HMGB1 in exogenous HMGB1-induced effects. Our findings could open new perspectives in developing an antifibrotic therapy by targetting the HSCs autophagy.

Abnormal Expression of Urea Transporter Protein in a Rat Model of Hepatorenal Syndrome Induced by Succinylated Gelatin.

BACKGROUND: Hepatorenal syndrome (HRS) is a serious complication of advanced chronic liver disease. Abdominal compartment syndrome (ACS) occurs with dysfunction of multiple organs when abdominal pressure increases. Here, we report on a novel model of ACS with ascites and a model of HRS in rats to observe the urea transporter protein (UT) expression in the 2 models. MATERIAL AND METHODS: A liver cirrhosis model was induced by CCl4. After changes of liver histopathology were observed, rats were injected intraperitoneally with succinylated gelatin to establish a model of ACS and HRS. Then, changes in BUN, Cr, and renal histopathology were detected. Moreover, the UT in ACS and HRS were also quantified. RESULTS: The surfaces of liver in the cirrhotic group became coarse, with visible small nodules and became yellow and greasy. The normal structure of the hepatic lobules were destroyed, and hyperplasia of fibrotic tissue and pseudo-lobe was observed. The levels of BUN and Cr were significantly increased in rats suffering from ACS and HRS, respectively, compared to their control groups. In addition, the mRNA levels of UT-A2 and UT-A3 decreased in rats with HRS compared to cirrhotic rats. However, there was no significant difference between the mRNA levels of UT-A2, UT-A3, and UT-B in rats with ACS vs. normal rats. CONCLUSIONS: It is feasible to model ACS in rats by injecting succinylated gelatin into the abdominal cavity. Increasing the intra-abdominal pressure by succinylated gelatin is also a novel approach for modeling HRS in cirrhotic rats. Compared with control rats, there is an abnormal mRNA expression of UT in ACS rats and HRS rats.

[Hepatopulmonary syndrome-related changes in D-dimer, prothrombin time, fibrinogen, CD4 and CD8 in a rat model system].

OBJECTIVE: To determine the changes in levels of D-dimer, prothrombin time (PT), fibrinogen (Fib), CD4 and CD8 in relation to hepatopulmonary syndrome (HPS) by using a rat model system and to assess the association with pathologic changes in lung. METHODS: Forty male Sprague-Dawley rats were divided into equal groups for modeling of cirrhosis and HPS. The two groups were assessed by blood gas analysis, standard biochemical tests to measure D-dimer, PT, Fib, CD4 and CD8, and pathological examination of lung tissues. RESULTS: The HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20+/-3.19 mmHg vs. 85.00+/-2.53 mmHg, P = 0.000). The HPS rats showed significantly higher levels of D-dimer, Fib and CD8 than the cirrhosis rats (0.39+/-0.09 mg/ml vs. 0.25+/-0.05 mg/ml, P = 0.000; 1.77+/-0.10 g/L vs. and 1.49+/-0.09 g/L, P = 0.010; 32.32+/-4.45/mm3 vs. 20.13+/-6.09/mm3, P = 0.014). The HPS rats showed significantly lower levels of PT, CD4 and CD4/CD8 than the cirrhosis rats (14.86+/-1.04 s vs. 16.23+/-0.75 s, P = 0.036; 20.45+/-3.86/mm3 vs. 26.75+/-5.32/mm3, P = 0.000; 0.64+/-0.09 vs. 1.32+/-0.13, P = 0.000). The lung tissues of the HPS rats showed microthrombosis in pulmonary vessels, which were not observed in lung tissues of the cirrhosis rats. CONCLUSION: HPS-related differential levels of D-dimer, PT, Fib, CD4, CD8 and CD4/CD8 may represent a biomarker profile suggestive of incidence of thromboembolism in lung.

High-level expression, purification and characterisation of porcine ß-defensin 2 in Pichia pastoris and its potential as a cost-efficient growth promoter in porcine feed.

Porcine ß-defensin 2 (pBD2), a recently discovered porcine defensin that is produced by the intestine, exerts antimicrobial activities and innate immune effects that are linked to intestinal diseases in pigs. Here, we report a codon-optimised protein corresponding to mature pBD2 cDNA that was expressed and purified in Pichia pastoris yeast. The highest amount of secreted protein (3,694.0 mg/L) was reached 144 h into a 150-h induction during high-density cultivation. Precipitation followed by gel exclusion chromatography yielded 383.7 mg/L purified recombinant pBD2 (rpBD2) with a purity of ~93.7 %. Two recombinant proteins of 5,458.5 and 5,258.4 Da were detected in the mass spectrum due to variation in the amino-terminus. The rpBD2 exhibited high antimicrobial activity against a broad range of pig pathogenic bacteria (minimal inhibitory concentration [MIC] 32-128 µg/mL); the highest activity was observed against Salmonella choleraesuis, Staphylococcus aureus and Streptococcus suis (MIC 32-64 µg/mL). However, rpBD2 also inhibited the growth of probiotics such as Lactobacillus plantarum, Bacillus subtilis and Saccharomyces cerevisiae, but at lower efficacies than the pathogens. Purified or unpurified rpBD2 also maintained high activity over a wide range of pH values (2.0-10.0), a high thermal stability at 100 °C for 40 min and significant resistance to papain, pepsin and trypsin. In addition, the activity of rpBD2 towards S. aureus was unaffected by 10 mM dithiothreitol (DTT) and 20 % dimethyl sulphoxide (DMSO). Our results suggest that pBD2 could be produced efficiently in large quantities in P. pastoris and be a substitute for traditional antibiotics for growth promotion in the porcine industry.

Effects of Cd2+ ions on root anatomical structure of four rice genotypes.

Root anatomical structures of four rice breeding materials (maintainer lines YixiangB and E2B, restorer lines R892 and Mianhui725), grown under different Cd2+ levels, were observed and the root resistance to Cd2+ ions was evaluated. Under low Cd stress, the new roots appeared in the cortex of four rice genotypes. The diameter of the new root in YixiangB was larger than that of E2B. The restorer line R892 generated more roots than Mianhui725. Under high Cd2+ stress, broken epidermis, damaged cortex and black spots appeared in both maintainer and restorerlines. In general, anatomical damages in the restorer lines (R892 and Mianhui725) were slighter than those of the maintainer lines (YixiangB and E2B). Thus, the restorer lines had more adaptive ability to Cd2+ stress than maintainer lines.

[A new strategy to establish a hepatopulmonary syndrome model in rats by inducing abdominal compartment syndrome in the presence of cirrhosis].

OBJECTIVE: To find a practical method to establish hepatopulmonary syndrome (HPS) in rats for use as an experimental model system. METHODS: Forty male Sprague-Dawley rats were equally divided into a normal group (injected subcutaneously with 3 mL/kg of olive oil for 12 weeks), abdominal compartment syndrome (ACS) group (injected subcutaneously with 3 mL/kg olive oil for 12 weeks, followed by an intraperitoneal injection of 4% succinylated gelatin and maintenance of 20 mmHg abdominal pressure for 3 h), cirrhosis group (injected subcutaneously with 40% carbon tetrachloride (CCl4) in olive oil twice weekly for 12 weeks, with first dose doubled), and an ACS+ cirrhosis (HPS model) group (CCl4-induced, followed by the intraperitoneal injection with succinylated gelatin and 3 h of 20 mmHg abdominal pressure). The mice were sacrificed to perform blood gas analysis and to assess lung pathology. Comparisons between two groups were carried out by non-parametric analysis, and multiple comparisons were carried out by the Kruskal-Wallis H test. RESULTS: Blood gas analyses showed significant differences in the values of pH for the normal group (7.41+/-0.04), the ACS group (7.22+/-0.06), the cirrhosis group (7.53+/-0.04), and the HPS model group (7.47+/-0.02) (P less than 0.05). The ACS group and the HPS model group showed significantly different values of partial pressure of oxygen (PaO2; 58.57+/-5.41 and 58.20+/-3.19 mm Hg) and of alveolar-arterial oxygen difference (AaDO2; 83.86+/-28.49 and 84.80+/-11.82 mm Hg) than the normal group and the cirrhosis group (PaO2: 86.67+/-1.37 and 85.00+/-2.53 mm Hg; AaDO2: 38.17+/-9.20 and 37.00+/-6.23 mm Hg) (P less than 0.05). Pathological analysis of the lungs from the ACS group revealed widened alveolar septa, different-sized alveolar spaces, reduced lung capacity, edema and hemorrhage in some of the alveolar cavities, and telangiectasia in the alveolar walls. The lungs from the cirrhosis group also showed widened alveolar septa, different-sized alveolar spaces, and reduced lung capacity, but were distinct in the features of inflammatory cell infiltration, and hyperemia in the pulmonary vessels. The lungs from the HPS model group showed all of the features of both the lungs from the ACS and cirrhosis groups, but also showed macrophage accumulation and microthrombi in the pulmonary vessels. CONCLUSION: Inducing ACS in the setting of CCL4-induced cirrhosis in a rat generates pathological features that adequately mirror those of HPS and may represent a useful experimental model for in vivo studies of HPS.

[Lung expression of tissue factor mRNA and its significance in a rat model of hepatopulmonary syndrome].

OBJECTIVE: To determine the lung expression of tissue factor (TF) mRNA in hepatopulmonary syndrome (HPS) using a rat model system and to investigate the potential significance of its differential expression. METHODS: Forty male Sprague-Dawley rats were used to establish models of cirrhosis (n = 20) and HPS (n = 20). Blood gas analysis was used to investigate the effects of each model on pulmonary function. Effects on the expression of TF mRNA in lung were determined by qRT-PCR and on lung pathology by histological analysis. RESULTS: The HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20 +/- 3.19 mmHg vs. 85.00 +/- 2.53 mmHg, P less than 0.05) but significantly higher TF mRNA expression in lung (0.77 +/- 0.22 vs. 0.33 +/- 0.14, P less than 0.05). TF mRNA expression was negatively correlated with the value of PaO2 (r = -0.565, P less than 0.05). The lungs of the cirrhosis rats showed widened alveolar intervals, diversified sizes of alveolar spaces, reduced lung capacity, inflammatory cell infiltration, and hyperemia in the pulmonary vessels. The lungs of the HPS rats showed all of the same changes but also with accumulated macrophages and micro-thrombosis in the pulmonary vessels. Among the HPS rats, those with micro-thrombosis in pulmonary vessels showed a greater increase in TF mRNA expression than those without (0.68 +/- 0.17 vs. 0.40 +/- 0.12, P less than 0.05). CONCLUSION: The expression of TF mRNA in lung of hepatopulmonary syndrome model rats was elevated and might increase the incidence of thromboembolism in the lung.

Does green finance and ICT matter for sustainable development: role of government expenditure and renewable energy investment.

Green financing and renewable energy growth are commonly influenced by public expenditure on health and R&D; however, data supporting this claim is scarce, especially in the 65 countries that are part of the Belt and Road Initiative (BRI). The study applied Augmented Mean Group (AMG) analysis on panel data from 2005 to 2018 for BRI nations to look at the interplay between R&D and health budgets, GDP growth, FDI, carbon emissions, green finance, and renewable energy deployment. This study uses the two models for green finance and renewable energy development. In the light of the first model, economic growth, public expenditures on health and R&D, and foreign direct investment cause to increase the level of green finance in BRI economies, while the emissions cause to reduce the level of green finance. Similarly, renewable energy development uses another explained variable by this study and found the positive contribution of growth, public expenditures, and FDI inflows to renewable energy development. In contrast, environmental pollution decreases the level of renewable energy development. In order to obtain the desired level of green finance and renewable energy development, policies are suggested by the study.

Understanding the role of green finance and innovation in achieving the sustainability paradigm: application of system GMM approach.

THe central challenge facing China's sustainable development is how to strike a balance between economic growth and environmental conservation. In China's ongoing economic revolution, green finance is more important than ever. The study empirically examined how green finance and innovation affect carbon emissions using panel data from 30 Chinese provinces gathered between 2010 and 2020. The empirical analysis is undertaken to utilize a series of methods to investigate the impact of green finance on carbon emissions. The findings show that increased green finance, innovation, and industrial structure reduce carbon output. Moreover, carbon emissions increase with increasing trade openness and economic growth. In order to achieve sustainable development goals through economic and environmental sustainability, it has been discovered that green finance can foster green technology innovation and green business.

[Application of serum total IgE, tryptase and chymase in the identification of death caused by drug anaphylactic shock].

OBJECTIVE: To explore the application value of serum total IgE, tryptase and chymase in the identification of death caused by drug anaphylactic shock. METHODS: The general information from 235 cases of non-drug anaphylactic shock and 32 cases of drug anaphylactic shock were analyzed. The serum IgE level had been detected in the cases. Ten cases caused by coronary disease and 10 cases caused by sudden manhood death syndrome were selected from non-drug anaphylactic shock cases for the control group. Expressions of tryptase and chymase in the lung and heart were detected using immunohistochemistry method. The number and IOD of positive mast cells were counted. RESULTS: In the drug anaphylactic shock group, the IgE value of 18 samples (56.25%) was significantly higher than the normal upper limit of 120 IU/mL. In the non-drug anaphylactic shock group, the IgE value of 67 samples (28.51%) was higher than 120 IU/mL. The expressions of tryptase and chymase were significantly increased in lung and myocardial tissue in drug anaphylactic shock group (P < 0.05). CONCLUSION: Tryptase and chymase are more superior than that of the serum total IgE in the diagnosis of death caused by drug anaphylactic shock, and are more suitable in forensic practice.

A non-invasive model based on the virtual portal pressure gradient to predict the first variceal hemorrhage in cirrhotic patients.

BACKGROUND AND AIMS: This study aimed to establish a non-invasive model based on the virtual portal pressure gradient (vPPG) to predict the first variceal hemorrhage (VH) in patients with cirrhosis. METHODS: This single-center study prospectively enrolled cirrhotic patients as the training and validation cohorts during different time periods. The PPG-detection software (PPGS 1.0) was used to perform vPPG calculation, which involves 2 steps including three-dimensional (3D) reconstruction of portal vein tree and subsequent application of computational fluid dynamics. All patients were given standard primary prophylaxis against VH and followed up for 2 years. Data from the training cohort were assessed using univariate and multivariate Cox regression and Kaplan-Meier analyses, by which a nomogram with its dynamic form was developed to estimate the probability of VH. RESULTS: In the training cohort (n = 128), 37 (28.9%) experienced VH during 2-year follow-up. Four variables including vPPG ≥ 10.5 mmHg (p < 0.001), PLT < 56 × 109/L (p = 0.048), albumin < 32 g/L (p < 0.001) and INR ≥ 1.2 (p = 0.022) were identified as independent risk factors of VH, among which vPPG showed the best diagnostic performance (AUC 0.875). Subsequently, these predictors were incorporated into the nomogram, of which C-indexes were 0.891 and 0.926 for the training and validation cohorts, respectively. Calibration curves demonstrated a great calibration ability of the model. At the threshold probabilities of 0.1-0.6 (1 year) and 0.1-1.0 (2 years), this nomogram could offer more net benefits in decision curve analysis. CONCLUSIONS: The vPPG-based nomogram could be used for risk stratification of the first VH in patients with cirrhosis.

Factors affecting cadmium accumulation in the soil profiles in an urban agricultural area.

Soil Cd pollution is a serious environmental issue associated with human activities. However, the factors determining exogenous Cd dynamics in the soil profile in a complex environment are not well understood. Based on regional observations from 169 soil profiles across the Chengdu Plain, this study explored the key factors controlling Cd accumulation in the soil profile under actual field conditions. Results showed that total soil Cd contents decreased from 0.377 to 0.196 mg kg-1 with increasing soil depth. The effects of phosphate fertilizer rates, road density and precipitation on the difference in total soil Cd content were only observed in topsoil, while agricultural land-use type and topography had no impact. In contrast, significant differences in the total soil Cd content among different parent material types were found in the 0-20, 40-60 and 60-100 cm soil depths. One sample t-tests showed that significant Cd accumulation occurred in the whole soil profile in soils formed from Q4 (Quaternary Holocene) grey alluvium, while soils formed from Q3 (Quaternary Pleistocene) old alluvium and Q4 grey-brown alluvium showed significant Cd accumulation only in the 0-40 cm soil layers. In the topsoil, acid soluble Cd accounted for the largest proportion of the total Cd in soils formed from Q4 grey alluvium, reducible Cd was the main fraction in soils formed from Q4 grey-brown alluvium, while reducible Cd and residual Cd contributed the largest proportion of the total soil Cd in soils formed from Q3 old alluvium. The above results indicated that parent material was the decisive factor determining the magnitudes and depths of exogenous Cd accumulation in the soil profile due to its impacts on the Cd fraction distributions. These findings suggested that the parent material-induced Cd fraction distributions and accumulation should be considered for effectively exploring targeted remediation strategies for Cd pollution.

Converting poultry litter to activated carbon: optimal carbonization conditions and product sorption for benzene.

To promote utilization of poultry litter as a source material for manufacturing low-cost activated carbon (AC) that can be used in wastewater treatment, this study investigated optimal production conditions and water-borne organic sorption potential of poultry litter-based AC. Pelletized broiler litter was carbonized at different temperatures for varied time periods and activated with steam at a range of flow rate and time. The AC products were examined for quality characteristics using standard methods and for organic sorption potentials using batch benzene sorption techniques. The study shows that the yield and quality of litter AC varied with production conditions. The optimal production conditions for poultry litter-based AC were carbonization at 700 degrees C for 45 min followed by activation with 2.5 ml min(-1) steam for another 45 min. The resulting AC possessed an iodine number of 454 mg g(-1) and a specific surface area of 403 m2 g(-1). It sorbed benzene in water following sigmoidal kinetic and isothermal patterns. The sorption capacity for benzene was 23.70 mg g(-1), lower than that of top-class commercial AC. The results, together with other reported research findings, suggest that poultry litter is a reasonable feedstock for low-cost AC applicable to pre-treat wastewater contaminated by organic pollutants and heavy metals.

Nomogram for predicting the risk of gastroesophageal varices after primary endoscopic prophylaxis for variceal hemorrhage in patients with cirrhosis.

BACKGROUND AND AIMS: The aim of this study was to identify predictors of non-high-risk gastroesophageal varices and evaluate the probability of the residual high-risk varices in cirrhosis patients after the primary endoscopic treatment. PATIENTS AND METHODS: Medical records of the patients with cirrhosis admitted for primary endoscopic prophylaxis gastroesophageal varices hemorrhage were retrospectively analyzed. The patients were divided into high-risk varices and non-high-risk varices groups according to the endoscopy. A nomogram was developed based on the results of multivariate Cox analyses. Accuracy of this model was validated by the concordance index (Harrell's c-index) and calibration curve. RESULTS: Altogether 117 patients were enrolled between March 2014 and April 2018. The multivariate Cox analyses identified spleen length <140 mm [odds ratio (OR) = 2.715; P = 0.037), small or medium size of esophageal varices (OR = 4.412; P = 0.017), unaccompanied with gastric varices (OR = 7.025; P = 0.003) and frequency of endoscopic variceal ligation ≥one time per 4 months (OR = 3.834; P = 0.034) as independent factors of non-high-risk varices. All significant predictors were incorporated into a nomogram to predict the residual high-risk varices, which showed a notable accuracy with the concordance index (0.833). CONCLUSION: The nomogram-based prediction of residual high-risk varices can be used for risk stratification in cirrhosis patients with gastroesophageal varices.

Lactobacillus casei protects intestinal mucosa from damage in chicks caused by Salmonella pullorum via regulating immunity and the Wnt signaling pathway and maintaining the abundance of gut microbiota.

Dysfunction of the intestinal mucosal barrier of chicks caused by Salmonella pullorum is of great harm to the poultry industry. Probiotics are recognized for their beneficial health-promoting properties, promoting maintenance of bowel epithelial integrity and host immune system homeostasis. Our previous research showed that Lactobacillus casei protects jejunal mucosa from injury in chicks infected with S. pullorum. However, the specific mechanisms underlying its protective properties are still not fully understood. In the present study, we aimed to explore the mechanisms underlying the protective effects of L. casei on the intestinal mucosal barrier of chicks infected with S. pullorum through histological, immunological, and molecular biology methods. The results indicated that L. casei significantly reduced the diarrhea rate, increased the daily weight gain, and maintained normal levels of IgA, IgM, and IgG in the serum of chicks infected with S. pullorum. Furthermore, we found that L. casei markedly improved the immunity of gut mucosa by regulating cytokine and chemokine receptor balance, elevating the number of intraepithelial lymphocytes, and hence effectively restraining bowel inflammation. Strikingly, feeding of infected chicks with L. casei notably boosted interleukin-22 expression to activate the Wingless-Int pathway, moderated diamine oxidase and D-lactic acid levels, diminished the generation of myosin light chain kinase, and expanded tight junction protein levels (Zonulin-1 and Claudin-1), strengthening the function of the gut mucosal epithelium. In addition, experiments using 16S rDNA sequencing also demonstrated that L. casei immensely weakened the adhesion of S. pullorum, mainly manifesting as improved diversity of the intestinal microbiota in the V4 area of infected chicks. Taken together, these results show that the application of L. casei may be a good strategy to regulate the intestinal inflammatory response of chicks infected with S. pullorum, providing new perspectives in producing antibiotic substitutes in poultry farms.

Significance of MR/OPN/HMGB1 axis in NAFLD-associated hepatic fibrogenesis.

AIMS: The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis, however non-alcoholic fatty liver disease (NAFLD) associated liver fibrogenesis have been poorly understood. We aimed to determine the significance of mineralocorticoid receptor (MR)/osteopontin (OPN)/high-mobility group box-1 (HMGB1) axis in this setting. MAIN METHODS: Liver specimens were collected from NAFLD patients and murine NAFLD models established with 12-week high fat diet (HFD) for analysis of both upstream signals of MR and intrahepatic MR/OPN/HMGB1 axis. The in vitro cell model of NAFLD-associated liver fibrogenesis was established by treating LX-2 (a cell line of human HSCs) with free fatty acids (FFA). The effects of MR signaling were evaluated using with ALD (MR activator) or eplerenone (Ep, MR antagonist). Moreover, the in vitro loss- and gain- of function approaches were applied to confirm the upstream and downstream relationships of mediators contained in the intracellular MR/OPN/HMGB1 axis of LX-2. KEY FINDINGS: In NAFLD condition, both human and mouse liver tissue samples demonstrated a significant up-regulation of MR/OPN/HMGB1 axis simultaneously with enhanced expression of pro-fibrogenic markers, including ACTA2, TIMP1, TGFB1 and COL1A1. Besides, enhanced production of serum aldosterone (ALD) was also observed in mouse NAFLD models. Moreover, the in vitro data demonstrated MR play an essential role in FFA-induced HSCs fibrogenesis. Meanwhile, MR acts as the upstream effector mediator of OPN and shares downstream HMGB1 with OPN. SIGNIFICANCE: The MR/OPN/HMGB1 axis could be therapeutically targeted to treat NAFLD associated hepatic fibrogenesis.

A new cytotoxic polycyclic polyprenylated acylphloroglucinol from Garcinia nujiangensis screened by the LC-PDA and LC-MS.

A new polycyclic polyprenylated acylphloroglucinol (1), nujiangefolin D, together with five known analogues (2-6), were isolated from the fruits of Garcinia nujiangensis. Compound 1 was screened by the LC-MS and LC-PDA. The structure of 1 was elucidated on the basis of extensive spectroscopic techniques including 1 D and 2 D NMR and MS analyses. The compounds isolated were evaluated for their cytotoxic activities against three cancer cell lines, 1 showed moderate cytotoxic activity against Hela, PANC-1, and MDA-MB-231 cell lines with IC50 values of 5.6 ± 0.1, 9.1 ± 0.2, and 8.3 ± 0.2 µM, respectively. The antitumor mechanism was explained via virtual docking of 1 to the main sites in the human serine/threonine-protein kinase mTOR (mTOR) crystal structure (PDB code: 4DRI). Furthermore, 1 may inhibit Hela cell proliferation through mTOR by the western blotting analysis. Taken together, 1 may be a potential mTOR inhibitor used for the treatment of cervical cancer.

Nutrient release from bisulfate-amended phytase-diet poultry litter under simulated weathering conditions.

Poultry litter generated on the Delmarva Peninsula is from phytase-modified bird diet and bisulfate amendment. To establish agronomic application rates in conservation tillage systems, bisulfate-amended phytase-diet poultry litter was investigated for its nutrient release kinetics and supply capacity under simulated weathering conditions. Delmarva poultry litter was packed in PVC columns (15 cm i.d. x 25 cm height) to a depth of 5 cm and leached intermittently with 600 mm of water for 190 days. Concentrations of various nutrients in leachate were analyzed and nutrient release kinetics were modelled. Poultry litter leachate contained high contents of dissolved organic carbon (DOC, 35-11,800 mg L(-1)), nitrogen (N 6-2690 mg L(-1)), phosphorus (P 45-225 mg L(-1)), potassium (K 20-6060 mg L(-1)), and other nutrients. Release of the nutrients occurred primarily in the starting 5 weeks and mostly followed a first order Exponential-Rise-to-Maximum model. Under the specified conditions, the poultry litter demonstrated a nutrient supply capacity of 11.7 kg N Mg(-1), 5.4 kg P Mg(-1), and 36.8 kg K Mg(-1). Release of the potentially plant-available N and K was nearly finalized within 190 days of leaching/weathering, but it would require two years for full release of the leachable P. The results indicate that with consideration of field conditions, surface application of bisulfate-amended phytase-diet Delmarva poultry litter at recommended 6.6 Mg ha(-1) to conservation tillage systems would largely provide P 25.0 kg ha(-1), N 106.6 kg ha(-1), and K 245.5 kg ha(-1) to seasonal crops.

The growing U.S. bioeconomy: Drivers, development and constraints.

Bioeconomy refers to economic activities using renewable biological resources to produce energy and domestic consumables. The U.S. bioeconomy emerged in the early 2000s as a result of the societal pursuit of energy independence and security, greenhouse gas emission mitigation and sustainable development. Founded on biotechnologies and stimulated by federal policies, the U.S. bioeconomy has been growing rapidly over the past decade. Intensive research and development endeavors have been carried out to explore advanced technologies for efficient biomass production, conversion, and valorization, through which numerous biotechnological innovations have been achieved to realize the commercial, cost-effective production of diverse transportation biofuels and high-value domestic bioproducts from various biomass feedstocks. The bioenergy products currently commercialized in the U.S. include bioethanol, biodiesel, biogas, bioheat and biopower; the commercialized bioproducts extend to biopolymers, biochemicals, biopharmaceuticals and bioadhesives. In 2017, more than 65.4 billion liters of biofuels and 2500 certified bioproducts were produced, creating 4 million job opportunities and sharing 2.5% of the U.S. economy. Commercial production of cellulosic ethanol, renewable diesel, green jet fuel and other advanced biofuels remains at the demonstration stage and needs further improvement in cost-competitiveness. Envisioning a Billion-Ton-Bioeconomy by 2030, the U.S. federal government has been implementing strategic activities to realize the goal. High costs of delivered biomass feedstock, immature biomass refinery technologies, lack of cost-comparative bioproducts, and low fossil fuel prices have been identified as the major constraints to a strong U.S. bioeconomy. To improve the bioeconomic viability, further biotechnological advances and integrated biorefinery processes are warranted.