IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms

Immunoglobulin E (IgE) activates mast cells (MCs). It remains unknown whether IgE also activates other inflammatory cells, and contributes to the pathogenesis of abdominal aortic aneurysms (AAAs). This study demonstrates that CD4+ T cells express IgE receptor FcεR1, at much higher levels than do CD8+ T cells. IgE induces CD4+ T-cell production of IL6 and IFN-γ, but reduces their production of IL10. FcεR1 deficiency (Fcer1a−/−) protects apolipoprotein E-deficient (Apoe−/−) mice from angiotensin-II infusion-induced AAAs and reduces plasma IL6 levels. Adoptive transfer of CD4+ T cells (but not CD8+ T cells), MCs, and macrophages from Apoe−/− mice, but not those from Apoe−/− Fcer1a−/− mice, increases AAA size and plasma IL6 in Apoe−/− Fcer1a−/− recipient mice. Biweekly intravenous administration of an anti-IgE monoclonal antibody ablated plasma IgE and reduced AAAs in Apoe−/− mice. Patients with AAAs had significantly higher plasma IgE levels than those without AAAs. This study establishes an important role of IgE in AAA pathogenesis by activating CD4+ T cells, MCs, and macrophages and supports consideration of neutralizing plasma IgE in the therapeutics of human AAAs

Cystatin C Deficiency Promotes Epidermal Dysplasia in K14-HPV16 Transgenic Mice

Cysteine protease cathepsins are important in extracellular matrix protein degradation, cell apoptosis, and angiogenesis. Mice lacking cathepsins are protected from tumor progression in several animal models, suggesting that the regulation of cathepsin activities controls the growth of various malignant tumors.We tested the role of cathepsins using a mouse model of multistage epithelial carcinogenesis, in which the human keratin-14 promoter/enhancer drove the expression of human papillomavirus type 16 (HPV16) early region E6/E7 transgenes. During the progression of premalignant dysplasia, we observed increased expression of cysteine protease cathepsin S, but concomitantly reduced expression of cathepsin endogenous inhibitor cystatin C in the skin tissue extract. Absence of cystatin C in these transgenic mice resulted in more progression of dysplasia to carcinoma in situ on the face, ear, chest, and tail. Chest and ear skin extract real time PCR and immunoblot analysis, mouse serum sample ELISA, tissue immunohistological analysis, and tissue extract-mediated in vitro elastinolysis and collagenolysis assays demonstrated that cystatin C deficiency significantly increased cathepsin expression and activity. In skin from both the chest and ear, we found that the absence of cystatin C reduced epithelial cell apoptosis but increased proliferation. From the same tissue preparations, we detected significantly higher levels of pro-angiogenic laminin 5-derived γ2 peptides and concurrently increased neovascularization in cystatin C-deficient mice, compared to those from wild-type control mice.Enhanced cathepsin expression and activity in cystatin C-deficient mice contributed to the progression of dysplasia by altering premalignant tissue epithelial proliferation, apoptosis, and neovascularization

EFFECTS OF CARBONATED RECYCLED CONCRETE AGGREGATE ON MECHANICAL PROPERTIES OF CONCRETE AND MICRO-PROPERTIES OF INTERFACIAL TRANSITION ZONE

The purpose of this paper was to study the effects of a carbonated recycled concrete aggregate (CRCA) on the mechanical properties of a recycled aggregate concrete (RAC) and the micro-properties of the interfacial transition zone (ITZ), and to determine their strengthening mechanisms. Recycled concrete aggregate (RCA) soaked with saturated lime water was treated by accelerated carbonation under a pressure of 0.30 MPa for 24 h, under the replacement ratios of 0%, 30%, 70%, 100%. The mechanical property tests included 7-day and 28-day compressive, splitting tensile, and flexural strength tests. The micro-property tests included scanning electron microscope-energy dispersive spectrometer (SEM-EDS), X-ray diffraction (XRD), and Vickers micro-hardness (VMH). The results showed that the pores of the old mortar (OM) and ITZ-2 in the CRCA were filled with calcite, which improved the properties of the CRCA. Therefore, with the replacement ratio of the CRCA, the improvement degrees of the mechanical properties of the RAC gradually increased. Furthermore, compared to the other phases in the RAC, ITZ-3 had the lowest properties, but had the highest improvement degree. Besides, the strengthening mechanism of the micro-properties of ITZ-3 by the CRCA can be explained by the nucleation and chemical effect of the calcite and the micro-bleeding effect of the ITZ-3. Namely, the calcite on the surface of the CRCA provided nucleation sites for the calcium silicate hydrate (C-S-H) and reacted with the aluminate in the ITZ-3 to form hemicarbonate (Hc) and monocarbonate (Mc). In addition, a decrease in the water absorption of the CRCA alleviated the micro-bleeding effect of the ITZ-3

UNIAXIAL COMPRESSIVE STRESS-STRAIN BEHAVIOUR OF RECYCLED AGGREGATE CONCRETE PREPARED WITH CARBONATED RECYCLED CONCRETE AGGREGATE

The influences of carbonated recycled concrete aggregate (CRCA) on the stress-strain behaviour of recycled aggregate concrete (RAC) were studied. Recycled concrete aggregate (RCA) pre-soaked in limewater was processed by accelerated carbonation for 24 h, whose pressure was 0.30 MPa. Four substitution ratios (0%, 30%, 70%, 100%) of the aggregate were utilised. RMT-150C rock mechanics test system (frame stiffness of 5 MN/mm, loading rate of 0.005 mm/s) was used to conduct the tests. The results showed that the failure modes of all specimens were shear failure, but the failure angles of RAC and CRAC (RAC prepared with CRCA) were larger than those of natural aggregate concrete (NAC), which were in the range of 63°-75° and 58°-64° respectively. As the substitution ratio of RCA increasing, the stress-strain curve of RAC gradually flattened, which meant its brittleness decreased. Moreover, its peak stress, elastic modulus, and peak strain decreased continuously, while its ultimate strain increased continuously. Compared with RAC, CRAC showed the similar stress-strain curve, but its brittleness was slightly higher. Furthermore, its peak stress, elastic modulus, and peak strain increased, while its ultimate strain decreased. Finally, based on linear regression analysis and relevant standards, the prediction models of peak stress, elastic modulus, peak strain, and ultimate strain, as well as the stress-strain constitutive models of RAC and CRAC were proposed, which had a good applicability to the test data. In conclusion, the stress-strain behaviour of CRAC were similar to that of RAC

Serum Magnesium Concentration Is Inversely Associated with Albuminuria and Retinopathy among Patients with Diabetes

Aim. To investigate the association between serum magnesium levels and microvascular complications among patients with diabetes. Methods. Patients with diabetes were recruited between April 2012 and January 2015. All patients received an assay of serum magnesium concentration, were screened for 24 h albumin excretion rate, and underwent nonmydriatic fundus photography. Albuminuria and retinopathy were defined accordingly. A total of 3,100 patients with normal serum magnesium levels were included in this study. Results. Patients with albuminuria and/or retinopathy had lower levels of serum magnesium than patients without these complications (P<0.001). The prevalence of isolated albuminuria, isolated retinopathy, and combined albuminuria and retinopathy decreased as the concentration of serum magnesium increased. Multiple logistic regression analysis indicated that the odds ratio for isolated albuminuria, isolated retinopathy, and concomitant albuminuria and retinopathy decreased by approximately 20% for every 0.1 mmol/L increase in serum magnesium concentration. Conclusion. Serum magnesium levels were negatively associated with the risk of diabetic microvascular complications among patients with serum magnesium levels within the normal range

Association Between Pancreatic Atrophy and Loss of Insulin Secretory Capacity in Patients With Type 2 Diabetes Mellitus

To examine pancreatic volume (PV) changes among patients with different duration of type 2 diabetes and whether pancreatic atrophy was associated with loss of insulin secretory capacity. Methods. This cross-sectional study (203 patients with type 2 diabetes, 93 controls without diabetes) was conducted from January 2016 to December 2017. Patients with type 2 diabetes were divided into 3 groups: recently diagnosed (duration≤2 years), midterm (duration 3-9 years), and long term (duration≥10 years). All the patients were scanned with upper abdominal computerized tomography; PV was then calculated by an experienced technician. Absolute insulin deficiency was defined as fasting C-peptide\u3c0.9 ng/mL. Results. Compared with PV (cm3) in the controls, the mean PV was similar in patients with recently diagnosed type 2 diabetes (68.8 versus 71.0, P=0.56) but significantly reduced in patients with midterm (68.8 versus 60.8, P\u3c0.05) and long-term (68.8 versus 53.1, P\u3c0.001) type 2 diabetes. A similar trend was observed for the PV index (PV adjusted for body surface area and body mass index). Furthermore, rates of pancreatic atrophy and absolute insulin deficiency increased with duration of diabetes. Multiple logistic regression analysis indicated that pancreatic atrophy was associated with higher likelihood of absolute insulin deficiency (odds ratio=4.47, 95%confidence interval=1.45-13.8). Conclusions. PV was reduced in those with midterm and long-term type 2 diabetes compared to individuals without type 2 diabetes. Overall, pancreatic atrophy was associated with the loss of insulin secretory capacity in patients with type 2 diabetes

Quantitative determination of zidovudine diaryl phosphate triester pro-drugs in rat plasma by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

A rapid, simple, and sensitive high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) method was developed and validated for quantitative analysis of 3'-azido-3'-deoxythyrmidine (zidovudine, AZT) diaryl phosphate triester pro-drugs, in rat plasma using 2',3'-dideoxy-2'3'-didehydrothymidine (d4T) as internal standard (IS). The analytes were extracted from rat plasma with methanol after protein precipitation. The compounds were separated by HPLC with gradient elution (on a Shim-pack VP-ODS C-18 analytical column using a mobile phase of methanol/10 mM ammonium acetate). All the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, recoveries and stability were determined. LLOQs were 10 ng mL(-1) for M1, M2, M3, M4. and M5, respectively. Cori-elation coefficient (r)values for the linear range of 10-10,000 ng mL(-1) were greater than 0.999 for all the analytes. The intra-day and inter-day precision and accuracy were higher than 7.13%. The relative and absolute recovery was above 72% and no matrix effects were observed for all the analytes. This validated method provides a modern, rapid, and robust procedure for the pharmacokinetic studies of the pro-drugs after intravenous administration to rats. Some important results of AZT diaryl phosphate triester pro-drugs concerning chemical effect on pharmacokinetic performance are also studied. (C) 2008 Elsevier B.V. All rights reserved.Major Program of National Natural Science Foundation of China [20732004]; People's Republic of China [2006DFA43030

The underlying processes of a soil mite metacommunity on a small scale

<div><p>Metacommunity theory provides an understanding of how ecological processes regulate local community assemblies. However, few field studies have evaluated the underlying mechanisms of a metacommunity on a small scale through revealing the relative roles of spatial and environmental filtering in structuring local community composition. Based on a spatially explicit sampling design in 2012 and 2013, this study aims to evaluate the underlying processes of a soil mite metacommunity on a small spatial scale (50 m) in a temperate deciduous forest located at the Maoershan Ecosystem Research Station, Northeast China. Moran’s eigenvector maps (MEMs) were used to model independent spatial variables. The relative importance of spatial (including trend variables, i.e., geographical coordinates, and broad- and fine-scale spatial variables) and environmental factors in driving the soil mite metacommunity was determined by variation partitioning. Mantel and partial Mantel tests and a redundancy analysis (RDA) were also used to identify the relative contributions of spatial and environmental variables. The results of variation partitioning suggested that the relatively large and significant variance was a result of spatial variables (including broad- and fine-scale spatial variables and trend), indicating the importance of dispersal limitation and autocorrelation processes. The significant contribution of environmental variables was detected in 2012 based on a partial Mantel test, and soil moisture and soil organic matter were especially important for the soil mite metacommunity composition in both years. The study suggested that the soil mite metacommunity was primarily regulated by dispersal limitation due to broad-scale and neutral biotic processes at a fine-scale and that environmental filtering might be of subordinate importance. In conclusion, a combination of metacommunity perspectives between neutral and species sorting theories was suggested to be important in the observed structure of the soil mite metacommunity at the studied small scale.</p></div