Angiogenic deficiency and adipose tissue dysfunction are associated with macrophage malfunction in SIRT1 \u3csup\u3e-/-\u3c/sup\u3e mice

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1 -/-) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1 -/-mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β)was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1 -/- mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1 -/- mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue. Copyright © 2012 by The Endocrine Society

Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated. Methods: The effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored. The possible molecular mechanism mediating this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2), transforming growth factor beta 1 (TGF-beta 1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced arthritis (CIA) in a mouse model were explored. Results: In vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-beta 1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. On the other hand, UC-MSCs induced hyporesponsiveness of T cells mediated by PGE2, TGF-beta 1 and NO and UC-MSCs could promote the expansion of CD4(+) Foxp3(+) regulatory T cells from RA patients. More importantly, systemic infusion of human UC-MSCs reduced the severity of CIA in a mouse model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-alpha, IL-6 and monocyte chemoattractant protein-1) and increased levels of the anti-inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice. Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA. Conclusions: In conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000287517000020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701RheumatologySCI(E)PubMed64ARTICLE6R2101

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: A randomised, double-blind, placebo-controlled trial

Objectives Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebocontrolled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. Methods A randomised, double-blind and placebocontrolled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. Results At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. Conclusions Low-dose IL-2 might be effective and tolerated in treatment of SThe work was supported by the National Natural Science Foundation of China (31530020,31570880,81471601,81601417 and 81701598), Peking-Tsinghua Center for Life Sciences to ZG LI, Beijing Sci-Tech Committee Z171100000417007,Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2019LCXQ013) supported by the Fundamental Research Funds for the Central Universities, Beijing Nova Program Z171100001117025, National Key Research and Development Program of China (2017YFC0909003 to DY), BellberryViertel Senior Medical Research Fellowship to DY and Beijing SL PHARM

Spectral Regression Based Fault Feature Extraction for Bearing Accelerometer Sensor Signals

Bearings are not only the most important element but also a common source of failures in rotary machinery. Bearing fault prognosis technology has been receiving more and more attention recently, in particular because it plays an increasingly important role in avoiding the occurrence of accidents. Therein, fault feature extraction (FFE) of bearing accelerometer sensor signals is essential to highlight representative features of bearing conditions for machinery fault diagnosis and prognosis. This paper proposes a spectral regression (SR)-based approach for fault feature extraction from original features including time, frequency and time-frequency domain features of bearing accelerometer sensor signals. SR is a novel regression framework for efficient regularized subspace learning and feature extraction technology, and it uses the least squares method to obtain the best projection direction, rather than computing the density matrix of features, so it also has the advantage in dimensionality reduction. The effectiveness of the SR-based method is validated experimentally by applying the acquired vibration signals data to bearings. The experimental results indicate that SR can reduce the computation cost and preserve more structure information about different bearing faults and severities, and it is demonstrated that the proposed feature extraction scheme has an advantage over other similar approaches

Identification of differentially expressed genes in sorghum (Sorghum bicolor) brown midrib mutants

Sorghum, a species able to produce a high yield of biomass and tolerate both drought and poor soil fertility, is considered to be a potential bioenergy crop candidate. The reduced lignin content characteristic of brown midrib (bmr) mutants improves the efficiency of bioethanol conversion from biomass. Suppression subtractive hybridization combined with cDNA microarray profiling was performed to characterize differential gene expression in a set of 13 bmr mutants, which accumulate significantly less lignin than the wildtype plant BTx623. Among the 153 differentially expressed genes identified, 43 were upregulated and 110 down regulated in the mutants. A semiquantitative RT–PCR analysis applied to 12 of these genes largely validated the microarray analysis data. The transcript abundance of genes encoding L-phenylalanine ammonia lyase and cinnamyl alcohol dehydrogenase was less in the mutants than in the wild type, consistent with the expectation that both enzymes are associated with lignin synthesis. However, the gene responsible for the lignin synthesis enzyme cinnamic acid 4-hydroxylase was upregulated in the mutants, indicating that the production of monolignol from L-phenylalanine may involve more than one pathway. The identity of the differentially expressed genes could be useful for breeding sorghum with improved efficiency of bioethanol conversion from lignocellulosic biomass

Wet Oxidation of AlxGa1-xAs/GaAs Distributed Bragg Reflectors

The wet oxidation of AlGaAs with high Al content in a distributed Bragg reflectors （DBR） is studied by scanning electron microscopy （SEM） and transmission electron microscopy （TEM）. Some voids distribute along the oxide/GaAs interfaces due to the stress induced by the wet oxidation of the AlGaAs layers. These voids decrease the shrinkage of the Al2O3 layers to 8% instead of the theoretical 20% when compared to the unoxidized AlGaAs layers. With the extension of oxidation time, the reactants are more completely transported to the front interface and the products are more completely transported out along the porous interfaces. As a result,the oxide quality is better

Geological features and exploration fields of tight oil in the Cenozoic of western Qaidam Basin, NW China

Using a large amount of drilling and experimental analysis data, this paper evaluates four potential fields of tight oil exploration in western Qaidam Basin from comprehensive analysis of geological conditions such as sedimentary environments, source rock evaluations, reservoir characteristics, and source-reservoir relationships. Influenced by continuous uplift of Tibet Plateau since Paleogene, the sedimentary environment of the western Qaidam Basin exibits three characteristics: (1) a paleo-topographic configuration consisted of inherited slopes, depressions and paleohighs; (2) frequent alternation of relative humid and arid paleoclimate; and (3) oscillation of salinity and level of the paleo-lake water. Preferential paleo-environment resulted in two sets of large-scale source rocks with high efficiency and two types of large-scale tight reservoir rocks (siliclastic and carbonate), deposited during the late Paleogene to early Neogene. The above source and reservoir rocks form favorable spatial relationships which can be classified into three categories: symbiotic, inter and lateral. Based on sedimentary environments and reservoir types, tight oil resource in western Qaidam Basin can be divided into four types, corresponding to four exploration fields: salty lacustrine carbonate tight oil, shallow lake beach-bar sandstone tight oil, delta-front-sandstone tight oil and deep lake gravity-flow-sandstone tight oil. The temporal and spatial distribution of tight oil has characteristics of layer concentration, strong regularity and large favorable area, in which the saline lacustrine carbonate and shallow lake beach-bar sandstone tight oil are the best exploration targets in the western Qaidam Basin. Key words: tight oil, geological features, exploration fields, Qaidam Basin, tight reservoi

Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus

Abstract. Background:. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients. Methods:. This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, i.e., with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis. Results:. Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8+ T cells (P = 0.005). In the multivariate logistic analysis, hyperuricemia and higher CD8+ T cells percentages were significantly correlated with hyperintense WM lesions in SLE patients (P = 0.019; OR 2.129, 95% confidence interval [CI] 1.313–4.006 and P < 0.001; OR 1.056, 95% CI 1.023–1.098, respectively). Conclusions:. Hyperintense WM lesions are common in SLE patients and significantly associated with systemic involvement, including NPSLE, LN, polyserous effusions, cardiac involvement, and disease damage. Hyperuricemia and a higher number of CD8+ T cells were independent factors associated with hyperintense WM lesions in SLE