Acute pancreatitis (AP) is considered a cascade of immune responses triggered by acinar cell necrosis. AP involves two main processes of systemic inflammatory response syndrome and subsequent ...compensatory anti-inflammatory response syndrome. Although great efforts have been made regarding AP therapy, the mortality rate of AP remains high. Secondary infection acts a lethal factor in AP. Lymphocytes act as major immune mediators in immune responses in the course of this disease. However, the relationship between lymphocytes and secondary infection in AP is unclear. This review summarizes the variation of lymphocytes and infection in AP. Knowledge of the characterization of circulating lymphocyte abnormalities is relevant for understanding the pathophysiology of AP.
The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5'-AMP-activated protein kinase, a key nutrient sensor for ...maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored. Here we show that AMPKα1 deficiency in the intestine results in weight gain and impaired glucose tolerance under high fat diet feeding, while metformin administration fails to ameliorate these metabolic disorders in intestinal AMPKα1 knockout mice. Further, AMPKα1 in the intestine communicates with brown adipose tissue to promote thermogenesis. Mechanistically, we uncover a link between intestinal AMPKα1 activation and BAT thermogenic regulation through modulating anti-microbial peptide-controlled gut microbiota and the metabolites. Our findings identify AMPKα1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin.
Alpinetin is a naturally occurring flavonoid from the ginger plants. We previously reported the identification of alpinetin as a ligand of human pregnane X receptor (hPXR). The current study ...investigated the role of alpinetin as a putative PXR activator in ameliorating chemically induced inflammatory bowel disease (IBD). We found that oral administration of alpinetin significantly alleviated the severity of dextran sulfate sodium (DSS)-induced colitis in mice by decreasing the inflammatory infiltration, the levels of the pro-inflammatory mediators, and the PXR target genes in the colon.
, alpinetin blocked the nuclear translocation of p-p65 in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Further, alpinetin significantly upregulated PXR target genes and inhibited TNF-α-induced NF-κB-luciferase activity in LS174T colorectal cells; however, this regulatory effects were lost when cellular PXR gene was knocked down. In PXR transactivation assays, alpinetin increased both mouse and human PXR transactivation in a dose-dependent manner. Ligand occluding mutants, S247W/C284W and S247W/C284W/S208W, in hPXR-reporter assays, abrogated alpinetin-induced hPXR transactivation. Finally, alpinetin bound to the hPXR-ligand-binding domain (LBD) was confirmed by competitive ligand binding assay. The current study significantly extends prior observations by validating a PXR/NF-κB regulatory mechanism governing alpinetin's anti-inflammatory effects in a murine model of IBD.
Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We recently reported the identification of isorhamnetin as an activator of the human pregnane X receptor (PXR), a known ...target for abrogating inflammation in inflammatory bowel disease (IBD). The current study investigated the role of isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced IBD. Using two different models (ulcerative colitis like and Crohn's disease like) of experimental IBD in mice, we demonstrated that isorhamnetin abrogated inflammation through inhibiting the activity of myeloperoxidase, the levels of TNF-α and IL-6, the mRNA expression of proinflammatory mediators (iNOS, ICAM-1, COX2, TNF-α, IL-2 and IL-6) and the phosphorylation of IκBα and NF-κB p65. PXR gene overexpression inhibited NF-κB luciferase activity, and the inhibition was potentiated by isorhamnetin treatment. PXR knockdown by siRNA demonstrated the necessity for PXR in isorhamnetin-mediated up-regulation of xenobiotic metabolism genes. Ligand pocket-filling mutants (S247W/C284W and S247W/C284W/S208W) of human PXR weakened the effect of isorhamnetin on PXR activation. Molecular docking studies and time-resolved fluorescence resonance energy transfer competitive binding assays confirmed the ligand (isorhamnetin)-binding affinity. These results clearly demonstrated the ameliorating effect of isorhamnetin on experimental IBD via PXR-mediated up-regulation of xenobiotic metabolism and down-regulation of NF-κB signaling. The novel findings may contribute to the effective utilization of isorhamnetin or its derivatives as a PXR ligand in the treatment of human IBD.
Combining freshwater consumption and wastewater emissions into a unified analysis framework and utilizing the epsilon-based measure (EBM) model with the characteristics of radial model and non-radial ...model, this paper evaluates green water use efficiency (GWUE) of 11 provincial-regions in the Yangtze River Economic Belt (YREB) and investigates its spatiotemporal differences during the period 2005-2014, on basis of which the contribution rate of each input-specific green water use inefficiency in the overall green water use efficiency and the potential of freshwater-saving and wastewater emissions reduction are also calculated. The Theil index is used to explore the sources of the provincial gap of green water use inefficiency, and a random-effect panel Tobit model is applied to test the impact of the influencing factors of green water use inefficiency in the YREB. It is found that green water use inefficiency of the YREB is relatively low and regional differences is significant during the sample period, indicating a large potential of water-saving and water pollution reduction, and narrowing BGAP and WGAP of the Upstream is the key for improving green water use inefficiency in the YREB. The panel Tobit regression results show that economic development, technological innovation, water use structure, water resources endowment, environmental regulation and regional differences all play positive/negative effects on green water use inefficiency in the YREB, while these factors' influencing direction, degree and significance are significantly different. The conclusions of our study can provide considerably valuable information for the YREB to reserve water resources and reduce wastewater emissions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute pancreatitis (AP) is pancreatic or systemic inflammation without or with motion organ dysfunction. Severe acute pancreatitis (SAP) is the main cause of death for patients with AP. A ...pro-/anti-inflammatory imbalance is considered the key regulation of disease severity. However, the real mechanism of SAP remains unclear. This study aimed to identify the frequency and specific roll of myeloid-derived suppressor cell (MDSC) in AP. We evaluated MDSC frequency and disease severity by analyzing MDSCs in the peripheral blood of healthy controls (HCs) and patients with mild acute pancreatitis (MAP) and SAP by flow cytometry. We also compared the frequency and inhibitory ability of MDSCs from HCs and SAP, and finally detected the reason for the difference in inhibitory ability. AP was marked by expansion of MDSCs as well as its subsets, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). The proportion of MDSC in the peripheral blood mononuclear cells of patients with AP was increased and positively correlated with AP severity. The frequency of MDSC was decreased after treatment compared with pre-treatment. CD3+ T cells were remarkably inhibited by MDSC derived from the patients with SAP. In the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), the MDSCs from patients with SAP increased. These findings demonstrated that MDSCs expanded in the peripheral blood in patients with AP, especially in those with SAP. Moreover, the inhibitory ability of MDSCs was increased in the patients with SAP compared with that in the HCs. The enhanced suppressive function was possibly caused by an overexpression of Arg-1 and ROS.
Haloacetamides (HAcAms) as a new class of nitrogenous disinfection byproducts (N-DBPs) have been widely detected in drinking water and reclaimed water. Cytotoxicity and genotoxicity of monoHAcAms are ...determined by the leaving tendency of the halogens and decrease following a rank order of iodoacetamide (IAcAm) > bromoacetamide (BAcAm) ≫ chloroacetamide (CAcAm). However, the in vivo toxicity date for monoHAcAms is limited. In this study, hepatic oxidative stress and metabolomics responses in mice corresponding to monoHAcAms exposure were investigated. Exposure to the monoHAcAms decreased the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the levels of malonaldehyde (MDA) and increased the level of 8-hydroxy-2-deoxyguanosine (8-OHdG), indicating that each exposure generated oxidative stress in mice liver. Metabolomic alterations were also induced by each monoHAcAms exposure. In addition, disruptions of metabolic pathways, related to amino acid, energy and lipid metabolism, were identified based on the significantly changed metabolites. These data, for the first time, provide a comprehensive view for the toxic effects of monoHAcAms.
Mosquito-borne diseases affect over half of the human population globally. Multiple studies have shown that chemical insecticides are ineffective because of resistance. Therefore, environmentally ...safe mosquito population control tools need to be developed. Ribonucleic acid interference (RNAi) is a reverse genetic mechanism recently introduced as a new pest control tool. This technique represents a new class of biorational technology that could combat the increased global incidence of insecticide resistance. The technique has the potential of becoming a critical component of integrated vector control programs. A 3-hydroxykynurenine transaminase (3-HKT) RNAi expression plasmid was constructed, generated and transformed into Chlamydomonas and Chlorella algae. The transgenic algae were then used to feed Ae. aegypti mosquito larvae. The feeding experiments were conducted on a small and large scale with 10 and about 300 larvae, respectively. The mortality rate of the larvae was calculated over 30 days. In addition, histological examination of the insect tissues was performed to examine the extent of tissue damage. The integumentary system and midguts of larvae fed with transgenic Chlamydomonas were severely damaged. The mortality rate of the larvae fed with transgenic Chlamydomonas ranged from 60 to 100% in small-scale tests. The survival rate of adult mosquitoes was 0.0% in a large-scale feeding experiment when the larvae were fed with transgenic Chlamydomonas. Moreover, when the larvae were fed with transgenic Chlorella, the mortality rate ranged from 6.7% to 43% compared to that fed wild-type Chlorella. 3HKT RNAi transgenic algae are in some scales lethal to Ae. aegypti. The findings of this study indicate that technology based on microalgae RNAi may provide a new way to control mosquito populations.
The figure shows the TTC-DHA, main species of unsaturated fatty acids in microbial cell membrane at 5°C (%), and the AFM image of activated sludge strengthening with magnetic field which provides ...information about the cell membrane unsaturated fatty acid composition and low temperature response of microorganism enzymatic activity at 5°C. It is a concise and illustrative application of PLFA analysis to reflect the composition of activated sludge in response to a magnetic field.
•C16:1ω7c, C18:1ω7c and C18:1ω9c were the essential unsaturated fatty acids at 5°C.•MF increased the Gram-negative bacteria content to improve the cold adaptability.•Heteropolar MF enhancement is much more effective than that of the homopolar MF.
The strengthening effects of static (homopolar and heteropolar) magnetic fields (MF) on microorganisms were compared in activated sludge degrading organic matter at low temperature. The TTC dehydrogenase activity improved substantially through external heteropolar MF intensification, and led to the highest COD removal rate of 94.9% at 5°C. Phospholipid fatty acid analysis showed that C16:1ω7c, C18:1ω7c and C18:1ω9c were the essential unsaturated fatty acids in cell membrane at low temperature (4–15°C), accounting for the majority of the whole unsaturated fatty acids. The MF effect increased the Gram-negative bacteria content to improve the cold adaptability. Shannon–Wiener diversity analysis demonstrated the samples with heteropolar MF had a higher PLFA diversity index (1.17–1.25) than that with homopolar MF (0.89–1.13). AFM observation showed MF smoothed part of the microbial cell surface, with some remaining distinct protuberances. Heteropolar MF enhancement performance is much more effective than that of the homopolar MF with identical plate distance.
Low-carbon technology innovation of power grid is vital for grid enterprises to improve their competitiveness and resource utilization efficiency. In this paper, a novel tripartite evolutionary game ...theory is proposed to examine the behavioral strategies of government, banks, and the grid enterprises in the low-carbon power grid technology innovation cooperation. The evolutionary replication dynamics equations are presented to study evolutionary stable strategies (ESS) of participants. The meaningful simulation results are as follows: from the subsidy perspective, even if the government subsidies are phasing out, the ESS of the low-carbon grid technology cooperation still converges to the Pareto optimal equilibrium; from the cost perspective, the higher low-carbon technology innovation cost only slows down the evolution rate, while the higher business cost of carbon asset pledge credit and the lower incentive cost not only slow down the evolution rate but also change the evolution results. It shows that the business cost of carbon asset pledge credit has a greater impact on the evolution of the system than the incentive cost; from the benefit perspective, increasing the green revenue and the successful probability of the low-carbon technology innovation can both prompt the ESS to evolve to Pareto optimal state, and the effect of the former is greater than the latter. These results provide a theoretical guidance for government to promote the development of low-carbon technology innovation of power grid.
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