Aim: Atherosclerosis (AS) characterized as a chronic inflammatory disease. Multiple immune cells and inflammatory cytokines, such as high mobility group protein (HMGB1), regulatory T (Treg) cells, T ...helper (Th17) cells, and inflammation-related cytokines, play a key role in its pathophysiology. A large number of studies report that HMGB1 and Th17 cells may promote atherosclerosis progression, whereas Treg cells may play a protective role in atherosclerosis; thus, alterations in the Treg/Th17 ratio may exist in atherosclerosis diseases. Up till now, the relationships between HMGB1 levels and the Treg/Th17 ratio remain incompletely understood. The major purpose of this study was to investigate the relationship between HMGB1 levels and the Treg/Th17 ratio in patients with coronary artery atherosclerotic plaques. Methods: We enrolled patients with coronary atherosclerosis and normal coronary artery as the research subjects. Flow cytometry was used to analyze the Treg cells, the Th17 cells frequency, and the Treg/Th17 ratio. Otherwise, real-time polymerase chain reaction was used for assays the mRNA expressions of HMGB1, retinoic acid-related orphan nuclear receptor C (RORC), and forkhead-winged helix transcription factor (Foxp3). Moreover, enzyme-linked immunosorbent assays were used to detect the level of protein and cytokines, such as HMGB1, IL-10, TGF-β1, IL-17A, and IL-23. Results: Using flow cytometry, we observed a significantly increased of Th17 cell frequency, whereas Treg cell frequency significantly decreased in atherosclerotic patients. Consistently, the levels of RORC mRNA were significantly increased in coronary atherosclerosis (AS) group compared to normal coronary artery (NCA) group (P＜0.01). In contrast, the expression of Foxp3 mRNA was markedly lower in the AS group than in the NCA group (P＜0.01). Furthermore, we observed the serum concentrations of HMGB1, IL-17A, and IL-23 were significantly higher in the AS group than in the NCA group (P＜0.01, respectively), whereas the concentrations of serum IL-10 and TGF-β1 were significantly lower in the AS group than in the NCA group (P＜0.01, respectively). In addition, we also found that HMGB1 levels showed negative correlation with the Treg/Th17 ratio in the two groups (r=－0.6984, P＜0.01). Conclusions: The data in our study indicated that HMGB1 may promote atherosclerosis progression via modulating the imbalance in the Treg/Th17 ratio.
Silver-catalyzed cascade difunctionalization of N-(p-methoxyaryl)propiolamides coupled with dearomatization was achieved and used to regiospecifically construct a variety of phosphorylated ...aza-decenones bearing adjacent quaternary stereocenters under mild conditions in moderate to excellent yields.
A direct link between Ca
and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca
causes the re-distribution of a portion of the intracellular ...unesterified cholesterol to a pool that is not available to the SCAP-SREBP complex. The SREBP processing pathway in ER Ca
depleted cells remained fully functional and responsive to changes in cellular cholesterol status but differed unexpectedly in basal activity. These findings establish the role of Ca
in determining the reference set-point for controlling cellular lipid homeostasis. We propose that ER Ca
status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Obesity is a calorie‐excessive state associated with high risk of diabetes, atherosclerosis, and certain types of tumors. Obesity may induce inflammation and insulin resistance (IR). We found that ...the expression of interferon (IFN) regulatory factor 9 (IRF9), a major transcription factor mediating IFN responses, was lower in livers of obese mice than in those of their lean counterparts. Furthermore, whole‐body IRF9 knockout (KO) mice were more obese and had aggravated IR, hepatic steatosis, and inflammation after chronic high‐fat diet feeding. In contrast, adenoviral‐mediated hepatic IRF9 overexpression in both diet‐induced and genetically (ob/ob) obese mice showed markedly improved hepatic insulin sensitivity and attenuated hepatic steatosis and inflammation. We further employed a yeast two‐hybrid screening system to investigate the interactions between IRF9 and its cofactors. Importantly, we identified that IRF9 interacts with peroxisome proliferator‐activated receptor alpha (PPAR‐α), an important metabolism‐associated nuclear receptor, to activate PPAR‐α target genes. In addition, liver‐specific PPAR‐α overexpression rescued insulin sensitivity and ameliorated hepatic steatosis and inflammation in IRF9 KO mice. Conclusion: IRF9 attenuates hepatic IR, steatosis, and inflammation through interaction with PPAR‐α. (Hepatology 2013;58:603–616)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Li-S batteries are considered as one of the most promising battery systems because of their large theoretical capacity and high energy density. However, the "shuttle effect" of soluble polysulfides ...and sluggish electrochemical redox kinetics of Li-S batteries could cause a broken electrode structure and poor electrochemical performance. Herein, a high-performance and stable Li-S battery has been demonstrated by employing organo-polysulfide chain modified acetylene black (ABPS) as the coating layer on the separator. In addition to the traditional advantages of fast electron transport and polysulfide-interception ability of the carbon coating layer, the grafted organo-polysulfide chain endows the ABPS coating layer with permselectivity for lithium ion against polysulfides, electrocatalytic ability for the sluggish redox kinetics and self-repairing ability for the broken electrode. Hence, the battery prepared using an ABPS-coated separator delivers the best cycling performance (970 mA h g
−1
at 0.2 C after 100 cycles) and rate performance (805 mA h g
−1
at 2 C) as compared to the cells using acetylene black (AB)-coated or Celgard separators. Moreover, the Li-S battery prepared using an ABPS-coated separator exhibits a stable cycling performance at 1 C over 500 cycles with a low degradation of 0.04% per cycle, and a high coulombic efficiency (near 100%). Furthermore, as the sulfur loading was increased to 6.8 mg cm
−2
, the Li-S battery using the ABPS-coated separator still could deliver a high areal capacity of 6.03 mA h cm
−2
with a low electrolyte/sulfur ratio (E/S = 4, μL
electrolyte
mg
S
−1
) after 170 cycles. Significantly, ABPS is an effective coating layer material for improving and stabilizing Li-S batteries.
A novel carbon-coating layer material through grafting an organo-polysulfide chain on the carbon matrix (ABPS) was proposed for solving the sluggish electrochemical redox kinetics and repairing the broken electrode of high-loading Li-S batteries.
Background Sinus of Valsalva aneurysm is a rare cardiac anomaly, and the difference between Asian and Western countries in its occurrence is not well established. This study was designed to ...investigate the difference between Asian and Western patients. Methods Between September 1988 and February 2006, 83 patients with sinus of Valsalva aneurysm underwent surgical repair in our institute. The aneurysms originated from the right and noncoronary sinus in 74 and 9, respectively, and ruptured into the right ventricle in 52 patients, the right atrium in 30, and the left ventricle in 1. Ventricular septal defect (n = 38), aortic regurgitation (n = 21), and bicuspid aortic valve (n = 4) were the common coexisting anomalies. To compare the differences between Asian and Western patients in sinus of Valsalva aneurysm, 1049 cases (654 Asian patients versus 395 Western) were collected from the literature. Results Sixty-six patients were followed up for 9.6 ± 3.8 years. The cardiac function of 15 patients with aortic regurgitation was worse than that of those with no aortic regurgitation ( p < 0.05). There was no difference between the direct closure and the patch closure ( p > 0.05). Analysis of all collected cases revealed that aneurysm of the sinus of Valsalva in Asian patients compared with Western series is characterized by a higher incidence, more aneurysms originating from the right coronary sinus (85.8% versus 67.9%), more aneurysm rupture into the right ventricle (72.5% versus 60%), a higher incidence of association with ventricular septal defect (52.4% versus 37.5%), and lower incidence of association with bicuspid aortic valve (0.6% versus 7.8%). However, both Asian and Western patient series have similar incidence of combination with aortic regurgitation (33.6% versus 32.7%). Conclusions Long-term results of ruptured sinus of Valsalva aneurysm are associated with preoperative aortic regurgitation. The difference between Asian and Western patients with ruptured aneurysm of the sinus of Valsalva is significant.
Data quality issues have attracted widespread attentions due to the negative impacts of dirty data on data mining and machine learning results. The relationship between data quality and the accuracy ...of results could be applied on the selection of the appropriate model with the consideration of data quality and the determination of the data share to clean. However, rare research has focused on exploring such relationship. Motivated by this, this paper conducts an experimental comparison for the effects of missing, inconsistent, and conflicting data on classification and clustering models. From the experimental results, we observe that dirty-data impacts are related to the error type, the error rate, and the data size. Based on the findings, we suggest users leverage our proposed metrics, sensibility and data quality inflection point, for model selection and data cleaning.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background In-hospital medical complications are associated with poorer clinical outcomes for stroke patients after disease onset. However, few studies from China have reported the effect of these ...complications on the mortality of patients with acute ischemic stroke. In this prospective work, the China National Stroke Registry Study, we investigated the effect of medical complications on the case fatality of patients with acute ischemic stroke. Methods From September 2007 to August 2008, we prospectively obtained the data of patients with acute stroke from 132 clinical centers in China. Medical complications, case fatality and other information recorded at baseline, during hospitalisation, and at 3, 6, and 12 months after stroke onset. Multivariable Logistic regression was performed to analyze the effect of medical complications on the case fatality of patients with acute ischemic stroke. Results There were 39741 patients screened, 14526 patients with acute ischemic stroke recruited, and 11 560 ischemic stroke patients without missing data identified during the 12-month follow-up. Of the 11 560 ischemic patients, 15.8% （1826） had in-hospital medical complications. The most common complication was pneumonia （1373; 11.9% of patients）, followed by urinary tract infection and gastrointestinal bleeding. In comparison with patients without complications, stroke patients with complications had a significantly higher risk of death during their hospitalization, and at 3, 6 and 12 months post-stroke. Having any one in-hospital medical complication was an independent risk factor for death in patients with acute ischemic stroke during hospital period （adjusted OR=6.946; 95% CI 5.181 to 9.314）, at 3 months （adjusted OR=3.843; 95% C/3.221 to 4.584）, 6 months （adjusted OR=3.492; 95% CI 2.970 to 4.106）, and 12 months （adjusted OR= 3.511; 95% CI 3.021 to 4.080）. Having multiple complications strongly increased the death risk of patients. Conclusion Short-term and long-term outcomes of acute stroke patients are affected by in-hospital medical complications.
Obesity and related metabolic diseases associated with chronic low‐grade inflammation greatly compromise human health. Previous observations on the roles of interferon regulatory factors (IRFs) in ...the regulation of metabolism prompted investigation of the involvement of a key family member, IRF3, in metabolic disorders. IRF3 expression in the liver is decreased in animals with diet‐induced and genetic obesity. The global knockout (KO) of IRF3 significantly promotes chronic high‐fat diet (HFD)‐induced hepatic insulin resistance and steatosis; in contrast, adenoviral‐mediated hepatic IRF3 overexpression preserves glucose and lipid homeostasis. Furthermore, systemic and hepatic inflammation, which is increased in IRF3 KO mice, is attenuated by the overexpression of hepatic IRF3. Importantly, inhibitor of nuclear factor kappa B kinase beta subunit / nuclear factor kappa B (IKKβ/NF‐κB) signaling is repressed by IRF3, and hepatic overexpression of the inhibitor of κB‐α (IκBα) reverses HFD‐induced insulin resistance and steatosis in IRF3 KO mice. Mechanistically, IRF3 interacts with the kinase domain of IKKβ in the cytoplasm and inhibits its downstream signaling. Moreover, deletion of the region of IRF3 responsible for the IRF3/IKKβ interaction inhibits the capacity of IRF3 to preserve glucose and lipid homeostasis. Conclusion: IRF3 interacts with IKKβ in the cytoplasm to inhibit IKKβ/NF‐κB signaling, thus alleviating hepatic inflammation, insulin resistance, and hepatic steatosis. (Hepatology 2014;59:870–885)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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