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ObjectiveTo estimate the burden of potential productivity losses due to uncorrected and under-corrected presbyopia in LMICs among the working-age population in both the cross-sectional and longitudinal manner.MethodsWe extracted data for the prevalence of presbyopia from the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2019. Data for the gross domestic product (GDP) per capita were extracted from the World Bank database and Central Intelligence Agency's World Factbook. We introduced life table models to construct age cohorts (in 5-year age groups) of the working-age population (aged from 40 to 64 years old) in LMICs, with simulated follow-up until 65 years old in people with and without uncorrected presbyopia. The differences in productivity-adjusted life years (PALYs) lived and productivity between these two cohorts were calculated. The potential productivity loss was estimated based on GDP per capita. The WHO standard 3% annual discount rate was applied to all years of life and PALYs lived.ResultsIn 2019, there were 238.40 million (95% confidence interval [CI]: 150.92–346.78 million) uncorrected and under-corrected presbyopia cases in LMICs, resulting in 54.13 billion (current US dollars) (95% confidence interval [CI]: 34.34–79.02 billion) potential productivity losses. With simulated follow-up until retirement, those with uncorrected and under-corrected presbyopia were predicted to experience an additional loss of 155 million PALYs (an average loss of 0.7 PALYs per case), which was equivalent to a total loss of US$ 315 billion (an average loss of US$ 1453.72 per person).ConclusionsOur findings highlight the considerable productivity losses due to uncorrected and under-corrected presbyopia in LMICs, especially in a longitudinal manner. There is a great need for the development of enabling eye care policies and programs to create access to eye care services, and more healthcare investment in the correction of presbyopia in the working-age population in LMICs. This study could provide evidences for some potential health-related strategies for socio-economic development.

Liver malignancies include primary and metastatic tumors. Limited progress has been achieved in improving the survival rate of patients with advanced stage liver cancer and who are unsuitable for surgery. Apart from surgery, chemoradiotherapy, trans-arterial chemoembolization and radiofrequency ablation, a novel therapeutic modality is needed for the clinical treatment of liver cancer. Photodynamic therapy (PDT) is a novel strategy for treating patients with advanced cancers; it uses a light-triggered cytotoxic photosensitizer and a laser light. PDT provides patients with a potential treatment approach with minimal invasion and low toxicity, that is, the whole course of treatment is painless, harmless, and repeatable. Therefore, PDT has been considered an effective palliative treatment for advanced liver cancers. To date, PDT has been used to treat hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma and liver metastases. Clinical outcomes reveal that PDT can be considered a promising treatment modality for all liver cancers to improve the quality and quantity of life of patients. Despite the advances achieved with this approach, several challenges still impede the application of PDT to liver malignancies. In this review, we focus on the recent advancements and discuss the future prospects of PDT in treating liver malignancies.

Background The global burden of pancreatic cancer (PCa) continues to grow. Detailed data on PCa epidemiology are essential for policy-making and appropriate healthcare resource allocation. Methods Estimates of incidence, death and disability-adjusted life years (DALYs) of PCa from 1990 to 2017 were collected from the Global Burden of Disease Study 2017. Decomposition analysis was conducted to detect the contributing factors related to PCa incidence variation. The estimated annual percentage change (EAPC) was calculated to quantify the PCa epidemiology trends over a specified interval. Results Globally, the incidence of PCa cases increased by 129.1% to 447 664 664 (95% uncertainty interval (UI) 438 597–456 295), death increased by 125.2% to 441 082 082 (95% UI 448 960–432 833), and DALYs increased by 107.3% to 9 080 004 (95% UI 8 894 128–9 256 346) between 1990 and 2017. Relatively higher sociodemographic index (SDI) regions were observed with greater incidences, more deaths and a greater number of DALYs of PCa, but relatively lower SDI regions experienced a sharply increasing trend in these measures. Decomposition analysis indicated that the global increase in PCa incidence was driven by the aging population from 2007 to 2017, especially in higher SDI regions. In addition, a significant negative correlation was found between EAPC and ASIR (in 1990) (r = −0.56, P Conclusions PCa remains a major public health burden globally. The unfavorable trend in PCa suggesting that further study for prevention should be conducted to forestall the increase in pancreatic cancer.

Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.

The present study aims to evaluate the effect of the ethyl acetate extract of Cichorium (EAEC) as a novel photosensitizer in photodynamic therapy (PDT) of colorectal carcinoma (CRC) HCT116 and SW620 cells. The absorption and fluorescence spectra of EAEC were measured using a UV-vis spectrophotometer and fluorescence spectrophotometer, respectively. EAEC-induced reactive oxygen species (ROS) production in HCT116 and SW620 cells was detected using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and glutathione/glutathione disulfide (GSH/GSSG). The photo- and dark toxicities of EAEC were estimated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake and localization of EAEC were detected by confocal laser fluorescence microscopy. Annexin V-FITC/PI staining, Western blotting and immunofluorescence staining were used to assess apoptosis and autophagy. The antitumor activity of EAEC was confirmed in a xenograft model. Finally, effects on the PERK pathway were verified using qRT-PCR and Western blotting. EAEC displayed absorption and fluorescence emission peaks at 660 nm and 678 nm, respectively. EAEC induced ROS production in CRC cells. Assessment of dark toxicity showed that treatment with EAEC alone induced little cytotoxicity in CRC or normal cells but that EAEC-PDT induced significant photocytotoxicity in CRC cells in a time- and dose-dependent manner. After cellular uptake, EAEC was located in the mitochondria. Treatment with EAEC-PDT reduced xenograft tumor size. Further evaluation suggested that activation of the PERK pathway mediates these effects, as the apoptotic rate and autophagy flux increased markedly after EAEC-PDT. EAEC, a natural photosensitizer extracted from Cichorium, displays potential utility in PDT of CRC by targeting the PERK pathway.

The impact of portal hypertension (PH) on postoperative short-term outcomes and long-term survival in hepatocellular carcinoma (HCC) patients has lately been discussed controversially. This study aimed to explore the influence of PH on postoperative outcomes in HCC patients undergoing surgical resection.Patients undergoing hepatectomy for HCC from 2010 to 2014 were enrolled. The impact of PH on postoperative complications, posthepatectomy liver failure (PHLF) and overall survival (OS) was evaluated.A total of 355 HCC patients were enrolled; 129 (36.3%) experienced postoperative complications and 21 (5.9%) developed PHLF. PH was identified as an independent predictor of PHLF. Patients with PH experienced a higher incidence of complications and PHLF than patients without PH. On the Cox proportional hazards regression model, PH was verified as a risk factor of OS for BCLC stage 0/A and B patients. Patients without PH had significantly better long-term survival compared to patients with PH both in the total cohort and in cirrhosis subgroup.Liver resection in HCC patients with PH showed a significantly increased postoperative complications and PHLF, and revealed a decreasing long-term survival than non-PH patients. Besides, tumor burden also played an important role in determining the OS. However, due to the improvement in surgical technique and perioperative management, surgery was feasible in carefully selected HCC patients with PH.

Natural orifice specimen extraction surgery (NOSES) is especially suitable for colorectal surgery. Until now, most of the reports published were about laparoscopic NOSES, the reports about robotic NOSES are extremely rare. This study aims to explore the safety and feasibility of robotic NOSES for colorectal neoplasms. All patients underwent robotic NOSES from March 2016 to October 2019 in our hospital were enrolled for retrospective analysis. Clinicopathological data including patient characteristics, perioperative information and pathological information were collected and analyzed. According to the distance between tumor and anus or whether neoadjuvant chemoradiotherapy (nRCT) is performed, we grouped the cases and studied its influence on robotic NOSES. Also, we compared the previous reports on laparoscopic NOSES with our study and revealed advantages of robotic NOSES in terms of safety and feasibility. A total of 180 patients were enrolled. The average distance from the lower edge of the tumor to the anus was (8.64 ± 3.64) cm and maximum circumferential diameter (CDmax) of specimen was (3.5 ± 1.6) cm. In terms of safety, the average operation time, intraoperative blood loss, and postoperative hospital stay were (187.5 ± 78.3) min, (47.4 ± 34) mL, and (11.3 ± 7.5) days, respectively. In terms of feasibility, the average number of lymph node harvested was (14.8 ± 5). Robotic NOSES shows advantages in terms of safety and feasibility compared with laparoscopic NOSES. This procedure could not only be a safe procedure but also could achieve good oncological outcomes.

Additional file 1: Figure S1. Phylogenetic tree of kinesin genes from C. lanatususing neighbor-joining method. Figure S2. Phylogenetic tree of kinesin genes from C. lanatusand and A. thaliana using neighbor-joining method. Figure S3. Phylogenetic tree of kinesin genes from C. lanatusand and S. lycopersicum using neighbor-joining method. Neighbor-joining phylogenetic tree of the kinesin family. The different kinesin subfamily was marked with different color, respectively. Figure S4. Comparative expression analysis of 5 ClKINsgenes in seed at different days after pollination by qRT-PCR. ClACTIN gene was used for normalization of quantitative RT-PCR results. The standard deviations of three biological replicates are represented by the error bars. Table S1. Kinesin gene family members identified in Citrullus lanatus. Table S2. The specific primers for qRT-PCR of 48 ClKINsgenes.

BACKGROUND Hepatocellular carcinoma (HCC) is the world’s sixth most common malignant tumor and the third cause of cancer death. Although great progress has been made in hepatectomy, it is still associated with a certain degree of risk of post-hepatectomy liver failure (PHLF), which extends the length of hospital stay and remains the leading cause of postoperative death. Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF. AIM To assess the value of model for end-stage liver disease (MELD) score combined with standardized future liver remnant (sFLR) volume in predicting PHLF in patients undergoing hepatectomy for HCC. METHODS This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018. Discrimination of sFLR volume, MELD score, and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve. RESULTS The patients were divided into two groups according to whether PHLF occurred after hepatectomy. The incidence of PHLF was 8.4% in our research. The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score. Both sFLR volume and MELD score were considered independent predictive factors for PHLF. Moreover, the cut-off value of the sFLR/MELD score to predict PHLF was 0.078 (P < 0.001). This suggests that an sFLR/MELD ≥ 0.078 indicates a higher incidence of PHLF than an sFLR/MELD < 0.078. CONCLUSION MELD combined with sFLR is a reliable and effective PHLF predictor, which is superior to MELD score or sFLR volume alone.

The present study aims to evaluate the effect of the ethyl acetate extract of

Supplemental Digital Content is available in the text, A precise and noninvasive method to predict posthepatectomy liver failure (PHLF) in clinical practice is still lacking. Liver fibrosis or cirrhosis accompanied with varying degrees of portal hypertension plays an important role in the occurrence of PHLF in hepatocellular carcinoma (HCC) patients. This study aims to compare the predictive ability of the albumin-bilirubin score to spleen thickness ratio (ALBI/ST) versus fibrosis-4 index (FIB-4) and aspartate aminotransferase to platelet count ratio index (ARPI) for the occurrence of PHLF. We retrospectively enrolled 932 patients who underwent liver resection for HCC between 2010 and 2017. The predictive accuracy of ALBI/ST ratio, FIB-4, and APRI for occurrence of PHLF was evaluated by receiver operating characteristic curve analysis. PHLF was diagnosed in 69 (7.4%) patients. The ALBI/ST ratio was found to be a significant predictor of PHLF. The AUC of ALBI/ST (AUC = 0.774; 95% CI, 0.731–0.817; P

Background Although robot-assisted distal pancreatectomy (RADP) has been successfully performed since 2003, its advantages over open distal pancreatectomy (ODP) are still uncertain. The objective of this meta-analysis is to compare the clinical and oncologic safety and efficacy of RADP vs ODP. Methods Multiple databases (PubMed, Medline, EMBASE, Web of Science, and Cochrane Library) were searched to identify studies that compare the outcomes of RADP and ODP (up to February, 2020). Fixed and random effects models were applied according to different conditions. Results A total of 7 studies from high-volume robotic surgery centers comprising 2264 patients were included finally. Compared with ODP, RADP was associated with lower estimated blood loss, lower blood transfusion rate, lower postoperative mortality rate, and shorter length of hospital stay. No significant difference was observed in operating time, the number of lymph nodes harvested, positive margin rate, spleen preservation rate, rate of severe morbidity, incidence of postoperative pancreatic fistula, and severe postoperative pancreatic fistula (grade B and C) between the 2 groups. Conclusions With regard to perioperative outcomes, RADP is a safe and feasible alternative to ODP in centers with expertise in robotic surgery. However, the evidence is limited and more randomized controlled trials are needed to further clearly define this role.

The Child-Pugh (CP) score is a widely used method to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the fibrosis index (FIB-4) has been demonstrated to be closely associated with liver fibrosis and cirrhosis. This study aimed to compare the capability of FIB-4 index with CP score in predicting the outcomes for HCC patients after hepatectomy. A total of 495 HCC patients who underwent hepatectomy were enrolled. The performance of the FIB-4 index in predicting postoperative liver failure (PHLF) and overall survival was compared with that of the CP score. Of them, 9.3% (46/495) patients developed PHLF. The area under the receiver operating characteristic (ROC) curve of the FIB-4 index for predicting PHLF was greater than that of the CP score (0.744 versus 0.621; P = 0.044). The optimal cutoff value of the FIB-4 index for predicting PHLF was 4.16. Multivariable analyses revealed that the FIB-4 index was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the CP grade was only a significant predictor of PHLF in the minor hepatectomy subgroup. The FIB-4 index (4.16) stratified patients into two distinct overall survival cohorts (P = 0.006). The FIB-4 index also classified patients with the Barcelona Clinical Liver Cancer (BCLC) stages 0 and A into two distinct overall survival cohorts (P = 0.001 and P = 0.034, respectively). The FIB-4 index may be a better predictor of PHLF and overall survival in HCC patients with hepatectomy than CP score.

Background Inflammatory bowel disease (IBD) is a group of inflammatory conditions characterized by chronic inflammation of the gastrointestinal (GI) tract. Recent preclinical and clinical studies have shown the therapeutic value of photodynamic therapy with low doses of photosensitizer and/or light in colitis treatment, but the detailed mechanism is unclear. Methods We examined 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy (PDT) in dextran sulfate sodium (DSS)-induced colitis in mice. Endoscopic and macroscopic observations as well as the Disease Activity Index score (DAI) was used to monitor the disease. Cytokine expression was measured by quantitative RT-PCR analysis to evaluate the efficacy of PDT. We applied the Clariom™ D bioinformatics analysis to investigate the differentially expressed genes after PDT. Finally, we used quantitative RT-PCR analysis and Western blotting to validate the targets of differentially expressed genes. Results 5-ALA-PDT improved the DAI score and decreased the expression of various inflammatory cytokines. The Clariom™ D bioinformatics analysis identified 2043 diff ;erentially expressed genes (702 up-regulated and 1341 down-regulated). We confirmed the down-regulation of lncRNA-Neat1, lncRNA-Snhg5 and lncRNA-Gm9926 and the up-regulation of miRNA-204-5p, miRNA-218-5p, miRNA-200a-3p and miRNA-466h-5p. Additionally, the decreased expression level of the AKT3, p-AKT3, PI3K, p-PI3K protein were confirmed. Conclusions This study provides in vivo comprehensive lncRNA and miRNA microarray analysis after 5-ALA-PDT treatment in DSS-induced colitis, and it may help to develop novel lncRNA-miRNA-related therapeutic approaches, such as the Neat1-miRNA204-5p-PI3K-AKT axis, to further increase the efficiency of PDT in IBD.

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Background: CD4+CD25+FoxP3+ regulatory T cells (Treg cells) play a protective role against the development and progression of the inflammatory disease atherosclerosis (AS). MicroRNA-21 (miR-21) is expressed in Treg cells and is up-regulated in the context of AS and other inflammatory diseases. Aims: This study aimed to determine the role of miR-21 in Treg cell regulation and gene expression during the development of AS in patients with coronary heart disease (CHD). Methods and Results: MiR-21 expression in peripheral blood mononuclear cells (PBMCs) was significantly up-regulated in patients with CHD (acute myocardial infarction (AMI) group, n=24; unstable angina (UA) group, n=21; stable angina (SA) group, n=24) compared with patients with chest pain syndrome (CPS, n=27), and miR-21 expression showed an increasing trend from SA to UA to AMI patients. Moreover, flow cytometry analysis indicated that the frequencies of circulating Treg cells decreased in a manner proportionate opposite with the level of miR-21. Quantitative real-time PCR (qRT-PCR) revealed a decrease in mRNA expression of forkhead box P3 (foxp3), transforming cell growth factor beta 1(TGF-β1) and smad7 (a known target gene of miR-21). ELISA analysis revealed a decrease in TGF-β1 secreted into the plasma. In addition, we transfected PBMCs with a miRNA negative control (NS-m), a miR-21 mimic (miR-21-m), a miRNA inhibitor negative control (NS-i), or a miR-21 inhibitor(miR-21-i). Up-regulation of miR-21 decreased the frequency of circulating Treg cells, decreased the expression levels of foxp3, TGF-β1 and smad7, and decreased the amount of TGF-β1 secreted into the plasma. Consistent with these observations, miR-21 down-regulation increased the frequency of circulating Treg cells, increased the expression of foxp3, TGF-β1 and smad7, and increased the amount of TGF-β1 secreted into the plasma. Conclusions: Because the smad7 expression pattern was similar to that of TGF-β, our study suggests that miR-21 can negatively regulate the frequency of circulating Treg cells through a TGF-β1/smad-independent signaling pathway in PBMCs.

The spin-polarized electronic properties for a zigzag-edge graphene nanoribbon (ZGNR) with an extended line defect are investigated, particularly focusing on controlling the effects of an external transverse electric field ( E ext ). An ab initio scanning tunneling microscope image for the defective ZGNR is also predicted. Results show that such a ZGNR can exhibit a strong spin polarization and ferromagnetic state, and the spin-filter effect can be significantly tuned and improved by the E ext . The spin-filter efficiency for our proposed device is predicted to be able to reach up to 60–81% in a large bias range of 0–0.6 V at E ext = 3.0 V/nm. Mechanisms for such results and the experimental feasibility for the device are suggested. These findings suggest a new possibility for developing nanometer-scale all-carbon spintronic devices.

Lovastatin is a member of Statins, which are beneficial in a lot of immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles in the activation and proliferation of T cells, and have become attractive target for immune-related disorders. The present study was designed to examine the block effect of Lovastatin on Kv1.3 channel in human T cells, and to clarify its new immunomodulatory mechanism. We found that Lovastatin inhibited Kv1.3 currents in a concentration- and voltage-dependent manner, and the IC50 for peak, end of the pulse was 39.81 ± 5.11, 6.92 ± 0.95 μM, respectively. Lovastatin also accelerated the decay rate of current inactivation and negatively shifted the steady-state inactivation curves concentration-dependently, without affecting the activation curve. However, 30 μM Lovastatin had no apparent effect on KCa current in human T cells. Furthermore, Lovastatin inhibited Ca2+ influx, T cell proliferation as well as IL-2 production. The activities of NFAT1 and NF-κB p65/50 were down-regulated by Lovastatin, too. At last, Mevalonate application only partially reversed the inhibition of Lovastatin on IL-2 secretion, and the siRNA against Kv1.3 also partially reduced this inhibitory effect of Lovastatin. In conclusion, Lovastatin can exert immunodulatory properties through the new mechanism of blocking Kv1.3 channel.

Interleukin-27 (IL-27) is an important cytokine in inflammatory diseases, including coronary artery disease (CAD). To explore the precise role of IL-27 in CAD, we investigated the genetic association between IL27 and CAD in the GeneID Chinese Han population. A two-stage case control association analysis was performed for 3075 CAD cases and 2802 controls. Logistic regression analysis was used to adjust the traditional risk factors for CAD. Results showed that a promoter variant, rs153109, tended to be marginally associated with CAD in the discovery population (Padj = 0.028, OR = 1.27, 95%CI: 1.03–1.58). However, this association was not replicated in the validation stage (Padj = 0.559, OR = 1.04, 95%CI: 0.90–1.21). In addition, when we classified the combined population into two subgroups according to the age at disease onset or disease state, we again obtained no significant associations. Finally, we estimated the severity of coronary stenosis using the Gensini Scoring system and determined that the rs153109 genotypes were still not associated with the Gensini scores of the CAD patients. In conclusion, our study failed to find an association between common variants in the functional region of IL27 and CAD in a Chinese Han population, which indicated that IL-27 might only be an inflammatory marker during the development of CAD.

Objective To explore potential relations between the intake of milk or dairy products and the risk of bladder cancer. Methods Eligible studies published up to May 2011 were retrieved via both computer searches and manual review of references. Random-effects models were used to calculate summary relative risk estimates (SRRE) based on high-contrast to low-intake values. Sensitivity and influence analyses were conducted, and heterogeneity among study results was explored through stratified analyses by study design, gender, geographic region, year of publication, or whether or not adjustment for several confounders (ie, age, gender, body mass index, smoking, and total energy intake). Results We extracted data from 14 studies on milk (involving 4879 cases) and 6 studies on dairy products (3087 cases). The total study population was up to 324,241 individuals. Overall, there was no significant association between milk intake and bladder cancer (SRRE 0.89, 95% CI 0.77-1.02). However, an inverse association was found in the United States (SRRE 0.88, 95% CI .79-.99). In addition, no significant association was observed between consumption of dairy products and risk of bladder cancer (SRRE 0.95, 95% CI .71-1.27), though an inverse association was detected in the Japanese population (SRRE 0.56, 95% CI .40-.80). Conclusion There appears to be enough evidence to support the null hypothesis. The overall result was not statistically significant. The findings of this meta-analysis are not supportive of an independent relationship between the intake of milk or dairy products and the risk of bladder cancer. However, these findings are based on limited research. Further efforts should be made to confirm these findings.

Three-dimensional model of the parts of the extrusion extruder for leisure food is created as an illustrator, which could be adopted up to form an assemble facility to the whole set of the machine conveniently by a software of SolidWorks in the paper.Some key specific modeling procedures are proved to show the advantages of Solidworks overweigh AutoCAD in three-dimensional modeling technology. The method put an adaptable way to short the whole lifetime of industrial product design.

To determine the effects of interleukin (IL)-17A inhibition on experimental atherosclerosis.ApoE(-/-) mice were treated with either rat anti-mouse IL-17A, mouse anti-mouse IL-17A or isotype-matched control antibodies for 12 weeks (n=8-10 per group). Ldlr(-/-) mice were transplanted with IL-17A-deficient or wild type bone marrow (n=8 per group). Rat anti-mouse IL-17A treatment obviously reduced plaque size by 43% (p0.01) without evidence of reduced IL-17A signaling. In contrast, mouse anti-mouse IL-17A treatment and IL-17A deficiency in bone marrow cells did not alter lesion size despite significant reduction of IL-17A production.Inhibition of IL-17A signaling does not alter lesion development in Th1-biased C57BL/6 ApoE(-/-) and Ldlr(-/-) mice with already low levels of IL-17A production. Alteration of lesion development after repeated injections of rat anti-mouse IL-17A antibody in ApoE(-/-) mice could not be attributed to blockade of IL-17A signaling.

Atherosclerosis is a chronic inflammatory disease in which the renin-angiotensin-aldosterone system plays an important role. Evidence indicate that the angiotensin type 1 receptor blockers can suppress atherogenesis, but the exact mechanisms have not been fully elucidated. The study was undertaken to investigate the potential effects and molecular mechanisms of an angiotensin type 1 receptor blocker irbesartan on atherogenesis in high cholesterol-diet apolipoprotein E knock-out mice.Adult male apolipoprotein E knock-out mice were given normal diet or high cholesterol-diet and randomized to receive no treatment or irbesartan 10 mg kg(-1) d(-1) for 12 weeks. The apolipoprotein E knock-out mice with high cholesterol-diet were associated with a marked increase in atherosclerotic lesion area, plasma lipid and angiotensin II levels, as well as the expressions of angiotensin type 1 receptor in the aorta. High cholesterol-diet feeding increases the activity of NADPH oxidase subunits (p47(phox) and Rac), extracellular signal-regulated kinase 1/2, janus kinase 2, signal transducer and activator of transcription 3, nuclear factor-kappaB and the expression of tumor necrosis factor-alpha, interleukin 6, monocyte chemoattactant protein-1 and vascular cell adhesion molecule-1 in the aortas. These changes were suppressed in mice that were treated with irbesartan 10 mg kg(-1) d(-1), with no significant change in systolic blood pressure and plasma lipid levels.The results suggest that irbesartan can attenuate atherosclerosis, and this effect is partly related to the inhibition of oxidative stress and inflammatory signal transduction pathways which eventually leads to the decrease in the expression of inflammatory cytokines.

Aims: Increasing evidences confirm the role of immune activation in the pathogenesis of chronic heart failure (CHF). Regulatory T cells appear central to the control of immune homeostasis. We assessed

Aim Hyperhomocysteinemia (Hhcy) is an important and independent risk factor for atherosclerosis. Recent studies have shown that Poly (ADP-ribose) polymerase (PARP) activation may be associated with Hhcy-induced endothelial dysfunction, which is an important mechanism for Hhcy to affect atherosclerotic progress. Thus, we investigated whether PARP inhibitors may attenuate atheroscle-rotic plaque development in an Hhcy-induced experimental animal model with atherosclerosis. Methods Six-week-old homozygous apolipoprotein E-deficient (ApoE-/-) male mice fed a normal diet or high methionine diet randomly received intraperitoneal injections of 10 mg/kg 3-aminoben-zamide (3-AB, a PARP inhibitor) dissolved in phosphate-buffered saline (PBS), or physiological saline every other day for 12 weeks. Atherosclerotic lesion sizes and PARP activity were measured. Related inflammatory factors in atherogenesis were investigated by real-time quantitative PCR and Western blot analysis. Results Our data demonstrated that ApoE-/- mice fed a high methionine diet generated Hhcy, which subsequently increased the atherosclerotic lesion size significantly, promoted oxidative stress-associated DNA damage and PARP activation, then increased the expression of proinflammatory fac-tors within atherosclerotic plaques. Although PARP inhibition by 3-AB did not markedly inhibit plaque development in ApoE-/- mice with spontaneous hyperlipidemia by feeding a normal diet, it significantly reduced the atherosclerotic lesion size by 40% in Hhcy-induced atherosclerosis without affecting plasma homocysteine levels and lipid contents, effectively suppressed PARP activation, and inhibited nuclear translocation of nuclear factor-(kappa)B (NF-(kappa)B) and subsequent production of inflam-matory factors, such as vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattactant protein-1 (MCP-1). Conclusion Our results suggest that PARP inhibition attenuates atherosclerotic plaque development under hyperhomocysteinemic conditions, through the inhibition of PARP activation, nuclear NF-kappaB translocation and subsequent expression of inflammatory factors.

We investigated the possible protective effect of poly (ADP-ribose) polymerase (PARP) inhibition in preventing endothelial dysfunction induced by hyperhomocysteinemia (Hhcy). Sprague–Dawley rats were divided into Hhcy group, Hhcy + 3-aminobenzamide(3-AB) group, control group and control + 3-AB group. A high-methionine diet was given to induce hyperhomocysteinemia. In Hhcy + 3-AB and control + 3-AB groups, rats were injected intraperitoneally with 3-AB (inhibitor of PARP). After 45 days, ultrastructural changes of aortas were observed by transmission electron microscope. Vascular reactivity of thoracic aortic rings was measured in organ chambers. PARP activity was detected. The levels of plasma total homocysteine, nitrite/nitrate, endothelin (ET)-1 and malondialdehyde were assayed. Rats in Hhcy group developed severe hyperhomocysteinemia and significant loss of endothelial function as measured by both vascular rings and levels of nitrite/nitrate and ET-1. Malondialdehyde levels increased significantly in Hhcy rats compared with control rats. 3-AB improved Ach-induced, NO-mediated vascular relaxation and stabilized the level of nitrite/nitrate and ET-1. Obvious improvement of ultrastructure can be observed in Hhcy + 3-AB group. These results suggest that pharmacological inhibition of PARP prevents the development of endothelial dysfunction in rats with hyperhomocysteinemia which may represent a novel approach to improve vascular dysfunction associated with hyperhomocysteinemia.

Atherosclerosis is a chronic inflammatory disease, which is positively and negatively regulated by T helper (Th) 1 and Th2 lymphocytes, respectively. Recent findings indicate that suppressive oligodeoxynucleotides (ODNs) expressing TTAGGG motifs selectively reduce Th1 cytokine production and have been proven effective at blocking the development of organ-specific autoimmune diseases. In the current research, we hypothesized that suppressive ODNs may alter the development of atherosclerosis. Eight-week-old homozygous ApoE(-/-) male mice were injected with 300 mug ODNs A151 (TTAGGG) or nonspecific ODNs 1612. Atherosclerotic lesion sizes were dramatically reduced by ODNs A151, but not by nonspecific ODNs. MCP-1 and VCAM-1, which are the key inflammatory factors in atherogenesis, were significantly attenuated by the suppressive ODNs A151. In the splenic lymphocytes, FACS analysis showed ODNs A151 reduced the percentage of IFN-gamma-producing Th1 cells and slightly increased the percentage of IL-4-producing Th2 cells, indicating that suppressive ODNs skewed the Th1/Th2 balance toward Th2 inflammation in vivo. Furthermore, ODNs A151 down-regulated the phosphorylation of STAT1 and STAT4 and suppressed up-regulation of T-bet, a signal modulator for Th1, and didn't impact GATA-3 and STAT6, which are associated with a Th2 phenotype. Consistent with this in vivo observation, ELISA analysis demonstrated that ODNs A151 suppressed Th1 cytokines IFN-gamma and TNF-alpha, and augmented Th2 cytokines IL-4 and IL-10 in vitro. This study provides the first experimental evidence that suppressive ODNs inhibit the development of atherosclerosis through inhibition of the STAT1/4 and T-bet pathways, which further modulate the Th1/Th2 balance in vivo.

The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granulocyte-macrophage colony-stimulating factor plus interleukin-4 in the presence or absence of RAPA (20 ng/mL), and stimulated with lipopolysaccharide (LPS) for 24 h before cells and supernatants were collected. Surface phenotype of BMDCs was flow-cytometrically detected to determine the expression of maturation markers, MHC class II and CD86. Supernatants were analyzed for the production of IL-12 and IFN-gamma cytokines by using ELISA. BMDCs were co-cultured with T cells from Lewis rats and mixed lymphocyte reaction was assessed by MTT method. The morphology of BMDCs stimulated with LPS remained immature after RAPA pretreatment. RAPA significantly decreased the CD86 expression, impaired the IL-12 and IFN-gamma production of BMDCs stimulated with LPS, and inhibited the proliferation of allogeneic T cells. In conclusion, RAPA can inhibit the maturation of BMDCs stimulated with LPS in terms of the morphology, surface phenotype, cytokine production, and ability of BMDCs to stimulate the proliferation of allogeneic T cells in vitro.

Lovastatin is a member of Statins, which are beneficial in a lot of immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles in the activation and proliferation of T cells and have become attractive target for immune-related disorders. The present study was designed to examine the block effect of Lovastatin on Kv1.3 channel in human T cells and to clarify its new immunomodulatory mechanism. We found that Lovastatin inhibited Kv1.3 currents in a concentration- and voltage-dependent manner and the IC50 for peak, end of the pulse was 39.81 ± 5.11, 6.92 ± 0.95 μM, respectively. Lovastatin also accelerated the decay rate of current inactivation and negatively shifted the steady-state inactivation curves concentration-dependently, without affecting the activation curve. However, 30 μM Lovastatin had no apparent effect on KCa current in human T cells. Furthermore, Lovastatin inhibited Ca2+ influx, T cell proliferation as well as IL-2 production. The activities of NFAT1 and NF-κB p65/50 were down-regulated by Lovastatin, too. At last, Mevalonate application only partially reversed the inhibition of Lovastatin on IL-2 secretion and the siRNA against Kv1.3 also partially reduced this inhibitory effect of Lovastatin. In conclusion, Lovastatin can exert immunodulatory properties through the new mechanism of blocking Kv1.3 channel.

In this study, a chaotic analysis approach was applied to a time series composed of seismic moment of events occurred in mine of Dong Gaussian copper mine subordinate to Tong Ling Nonferrous Metals Group Co. In Anhui province, China. The chaotic attractor dimension and the largest lyapunov index were put forward to determine whether the seismic flow of rock is chaotic and the degree of chaos. The analysis of examples indicates the dynamics of the seismic flow of rock belong to the category of dissipative systems, which exhibit chaotic behavior.

To construct and characterize EGFP reporter gene labeled Sindbis virus (SINV).The reporter gene EGFP was inserted into the genome of infectious clone pBR-XJ160 by using multi-fusion long fragment PCR method. Then apply reverse genetic manipulation technique to rescue and obtain EGFP labeled SINV.We successively obtained labeled SINV, which has good fluorescent expression characteristics and genetic stability.The labeled virus can be seen in living cells and living body, and this serves as a good tool for cell and tissue tropism and biological function study of viruses. This study laid a foundation for further studying the cell tropism, biological functions and infection mechanism of SINV.

To investigate retrospectively the relationship between clinicopathological factors and lymph node matastasis of pancreatic adenocarcinoma.The clinicopathological factors, including gender, age, preoperative CA-19-9 level etc. of 71 patients with pancreatic adenocarcinoma were summarized to analyze the relationship between those factors and lymph node matastasis.Among the 71 cases, there were 49 males (69.0%) and 22 females (31.0%). Forty-eight were ≥ 60 (67.6%) and 23 were60 (32.4%) years old. Twenty patients had normal preoperative CA-19-9 level (28.2%) and 51 had elevated level (71.8%). The tumor in 43 (60.6%) cases located in the pancreatic head and neck, and 28 (39.4%) in the body and tail. The tumors in 8 patients were well-differentiated (11.3%), 27 were moderately differentiated (38.0%), and 36 were poorly differentiated (50.7%). The maximum diameter of the tumor was ≤ 2 cm in 11 cases (15.5%), 2 - 5 cm in 45 cases (63.4%), and5 cm in 15 cases (21.1%). Ten patients had tumor confined to the pancreas (14.1%), and 61 invaded peripancreatic tissues (85.9%). Vascular tumor thrombus was found in 48 cases (67.6%), and 23 cases were absent (32.4%). Thirty-six cases had lymph node matastasis (50.7%). Univariate chi-square test revealed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P0.05). Multivariate logistic regression analysis also showed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P0.05).The differentiation of tumor and range of local infiltration of pancreatic adenocarcinoma are significantly associated with lymph node metastasis. There is no significant relationship of location of the tumor, maximum diameter, presence or absence of vascular tumor thrombus with lymph node metastasis. Therefore, special attention should be paid to lymph node dissection in cases with a poorly differentiated pancreatic adenocarcinoma invading into peripancreatic tissues.

To construct the recombinant virus-like particles containing HCV envelope glycoprotein E1E2 based on sindbis virus vector.The gene encoding HCV envelope glycoprotein E1E2 was cloned into sindbis virus vector to construct recombinant plasmids pBR-XJE1E2 and pVA-XJE1E2, and transfect them into BHK-21 cells to obtain recombinant virus-like particles. The expression of E1 and E2 protein were verified by Western Blot and indirect immunofluorescent assay (IFA).The results of restriction enzyme digestion, PCR and sequencing analysis showed that the recombinant plasmids were constructed successfully. And the results of RT-PCR, Western blotting and IFA detection showed that the transfect cells could package HCV-like particles of expressing structural proteins E1E2.The recombinant expression plasmids pBR-XJE1E2 and pVA-XJE1E2 based on sindbis virus vector could package HCV-like particles in eukaryotic cell, which provides a foundation for further study of its in vivo animal immune response.

To investigate the necessity and potential application of structural genes for expressing heterogenous genes from Sindbis virus-derived vector, the DNA-based expression vector pVaXJ was constructed by placing the recombinant genome of sindbis-like virus XJ-160 under the control of the human cytomegalovirus (CMV) promoter of the plasmid pVAX1, in which viral structural genes were replaced by a polylinker cassette to allow for insertion of heterologous genes. The defect helper plasmids pVaE or pVaC were developed by cloning the gene of glycoprotein E3E26KE1 or capsid protein of XJ-160 virus into pVAX1, respectively. The report gene cassette pVaXJ-EGFP or pV-Gluc expressing enhanced green fluorescence protein (EGFP) or Gaussia luciferase (G.luc) were constructed by cloning EGFP or G.luc gene into pVaXJ. EGFP or G.luc was expressed in the BHK-21 cells co-transfected with report gene cassettes and pVaE at levels that were comparable to those produced by report gene cassettes, pVaC and pVaE and were much higher than the levels produced by report gene cassette and pVaC, suggesting that glycoprotein is enough for Sindbis virus-derived DNA vector to express heterogenous genes in host cells. The method of gene expression from Sindbis virus-based DNA vector only co-transfected with envelop E gene increase the conveniency and the utility of alphavirus-based vector systems in general.

The generalized Laguerre-generalized Hermite mixed spectral method is developed. Various orthogonal projections are investigated. Some mixed approximation results are established. As an example of their important applications, a mixed spectral scheme is proposed for two-dimensional non-isotropic heat conduction equation. Its convergence is proved. Numerical results demonstrate the high accuracy of this new spectral method.

Double crank four ring-plate-type pin-cycloidal gear planetary drive is a new-type drive with new drive principle. In order to reduce weight of the whole drive, the method of shape optimization of ring-plate in the double crank ring-plate-type pin-cycloidal gear planetary drive was derived. It bases on the principal idea of structural boundary strength optimization method, makes use of APDL in FEA software ANSYS, realizes automatically the description and dispersal of model, that is, the finite element mesh is divided automatically. This method is suitable for the shape optimization of engineering structural.

Introduction Statins have been shown to exert anti-inflammatory effects. The aim of this study was to investigate whether rosuvastatin has favorable effect on ventricular remodeling after myocardial infarction (MI), whether this effect is associated with tumor necrosis factor (TNF)-α expression and p38 mitogen-activated protein (MAP) kinase pathway and, furthermore, whether there is close correlation between gene expression of TNF-α and activity of p38 MAP kinase. Methods and Results Adult male Wistar rats with acute MI were randomly divided into 2 groups: (1) rosuvastatin-treated group (MI-R) receiving rosuvastatin 20 mg/kg once daily, and (2) infarcted group (MI) receiving saline, when compared with sham-operated control group. Four weeks later, echocardiography, hemodynamics and Van Gieson staining were applied to evaluate left ventricular remodeling and cardiac function. Myocardial gene expression of TNF-α and activity of p38 MAP kinase were analyzed by real time-polymerase chain reaction and Western blot, respectively. The results demonstrated that increased TNF-α gene expression in noninfarcted areas was accompanied by activation of p38 MAP kinase pathway. Moreover, treatment of rosuvastatin markedly improved ventricular remodeling and cardiac function in rats, which was associated with attenuations in both TNF-α gene expression and p38 MAP kinase activity in myocardium without changes in serum lipid levels. Conclusions Treatment of rosuvastatin was able to improve cardiac remodeling and cardiac function after acute MI, which was associated with attenuations in both expression of TNF-α and activity of p38 MAP kinase in myocardium.

Increasing evidences confirm the role of immune activation in the pathogenesis of chronic heart failure (CHF). Regulatory T cells appear central to the control of immune homeostasis. We assessed the hypothesis that the circulating frequency and function of CD4+CD25+ Foxp3+CD127(low) T regulatory cells (Tregs) would be deranged in patients with CHF.Ninety-nine CHF patients due to non-ischemic (NIHF) or ischemic etiology (IHF) and 24 control donors were enrolled in the study. Frequency of circulating Tregs was evaluated by flow cytometry. Foxp3 in peripheral blood mononuclear cells (PBMCs) was assayed at the mRNA level by real-time PCR. Functional properties of Tregs to suppress proliferation and pro-inflammatory cytokines secretion of activated CD4+CD25(-) T cells were measured by proliferation assay and ELISA.The results demonstrated that CHF patients had significantly lower frequency of circulating Tregs and reduced Foxp3 expression in PBMCs compared with control donors. Moreover, Tregs from CHF patients showed compromised function to suppress CD4+CD25(-) T cells proliferation and pro-inflammatory cytokines secretion. A similar pattern with reduced Tregs frequency and compromised function was found in both NIHF and IHF patients. Correlation analysis suggested that Tregs frequency and function positively correlated with LVEF, whereas negatively correlated with LVEDD and NT-proBNP in patients with CHF.Our data are the first to demonstrate that frequencies of circulating Tregs in patients with CHF are reduced and their suppressive function compromised independently of the etiology. Defective Tregs may be an underlying mechanism of immune activation in CHF patients.

Objective: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE −/− mice. Methods and results: Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE −/− mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE −/− mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (RORγt) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-β 1 ) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8–16 weeks of age) in ApoE −/− mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE −/− mice than in their age-matched wild-type littermates. Conclusions: Th17/Treg functional imbalance exists during atherogenesis in ApoE −/− mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis.

Rab family proteins play a crucial role in regulating vesicular traffic in eukaryotic cells. EoRab43 is an atypical Rab gene identified in Euplotes octocarinatus. In order to understand the function of EoRab43, the 153bp fragment of the 3'-end of EoRab43 gene was subcloned into expression vector pGEX-6P-1, and the recombinant plasmid pGEX-EoRab43(153bp) was transfered into E.coli BL21 (DE3) to express the fusion protein. The fusion protein GST-EoRab43C was expressed and purified by affinity chromatography. BALB/c mice were immunolized by purified GST-EoRab43C. The titer of anti-EoRab43C polyclonal antibody was detected by indirect ELISA assay and the specificity of the antibody was detected by Western blot. Immunofluorescence experiments were performed using anti-EoRab43C antibody in the cells of Euplotes. The results showed that EoRab43 displayed a punctuate pattern in the cytoplasm around the macronuclear chromosome of Euplotes.

According to the feature that Genetic Algorithm (GA) is adapted to requirement of Culture Algorithms (CA) framework, GA is as the population space of CA and these

Background The T-helper (Th)1/Th2 imbalance has been demonstrated to be involved in chronic heart failure (CHF). We sought to determine whether atorvastatin exhibited any effect on CHF through modulating the Th1/Th2 response. Methods and Results We measured serum concentrations of interleukin (IL)-12, -18, interferon (IFN)-γ, IL-4, and IL-10 from 20 controls and 72 patients with nonischemic CHF by enzyme-linked immunosorbent assay. To investigate the effect of atorvastatin in vivo, CHF patients were either classified into a usual therapy group (n = 35) or usual therapy plus atorvastatin (10 mg/day) group (n = 37). Patient serum levels of IFN-γ and IL-4 were measured at time of admission and 2 weeks after treatment. Peripheral blood mononuclear cells from patients of CHF group were cultured in the presence or absence of atorvastatin (0, 0.4, 1, and 4 μmol/L) in vitro, and IFN-γ and IL-4 levels were detected. Serum levels of IL-12, IL-18, and IFN-γ were significantly higher in the CHF group than in the control group. The levels of IFN-γ and the ratios of IFN-γ:IL-4 were significantly decreased with atorvastatin treatment both in vivo and in vitro, whereas levels of IL-4 did not differ significantly. Conclusions Th1 polarization exists in patients with CHF, and atorvastatin can modulate the Th1/Th2 response through inhibiting Th1 cytokine production.

Oxidative stress and inflammation processes are key components of atherosclerosis, from fatty streak formation to plaque rupture and thrombosis. Evidence has revealed that calcium-channel blockers (CCB) could retard atherogenesis, but the exact mechanisms have not been fully elucidated. The present study was undertaken to investigate the potential effects and molecular mechanisms of the CCB felodipine on the process of atherosclerosis in high-cholesterol-diet (HCD) apolipoprotein E-knockout (ApoE KO) mice. Adult male ApoE KO mice were given a normal diet (ND) or HCD and were randomized to no treatment or felodipine (5 mg / kg per day for 12 weeks). The ApoE KO mice with HCD were associated with a marked increase in plasma lipid levels, atherosclerotic lesion area, and the expressions of NADPH oxidase subunits (p47 and Rac-1), nuclear factor-kappaB (NF-kappaB) in nucleus, phosphor-inhibitors of kappaB (p-IkappaB), tumor necrosis-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and vascular cell-adhesion molecule-1 (VCAM-1). These changes were suppressed in mice that were treated with felodipine (5 mg/kg per day for 12 weeks) concomitant with HCD administration, with no significant change in systolic blood pressure and plasma lipid levels. The results suggest that felodipine can attenuate atherosclerosis, and this effect is partly related to inhibition of oxidative stress and inflammatory signal-transduction pathways, which lead to decreases in the expression of inflammatory cytokines.

Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4+CD25+Foxp3+ regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets from Th1 and Th2 cells and have the opposite effects on autoimmunity. Th17/Treg balance controls inflammation and may be important in the pathogenesis of plaque destabilization and the onset of acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)]. To assess whether this balance was broken in patients with coronary heart disease, we detected Th17/Treg functions on different levels including cell frequencies, related cytokine secretion and key transcription factors in patients with AMI, UA, stable angina (SA) and controls. The results demonstrated that patients with ACS revealed significant increase in peripheral Th17 number, Th17 related cytokines (IL-17, IL-6 and IL-23) and transcription factor (RORgammat) levels and obvious decrease in Treg number, Treg related cytokines (IL-10 and TGF-beta1) and transcription factor (Foxp3) levels as compared with patients with SA and controls. Results indicate that Th17/Treg functional imbalance exists in patients with ACS, suggesting a potential role for Th17/Treg imbalance in plaque destabilization and the onset of ACS.

Cross-border (MA enterprises - foreign enterprise (TNCs) and domestically-funded enterprise (host country's enterprise) will decrease their outputs, but the decrease of the former one will not exceed the latter; foreign investing enterprise can maintain, even increase its output when it involves in the Cournot competition with the domestic investing enterprise for the factor of corporate governance optimization; and different modes of government regulations will lead to different market structures.

C5H4Br2N2 ,m onoclinic, P21/n (no. 14), a =6 .07(1) A, b =1 0.53(2) A, c =1 1.89(2) A, / =1 04.49(3)°, V =7 36.0 A 3 , Z =4 , Rgt(F) =0 .0307, wRref(F 2 ) =0 .0795, T =2 96 K. Source of material Th ec ompoun dw as obtained commercially (Aldrich). 0.5 mg of the compound was dissolve di n1 0m lo fm ethanol. The solution wa sl ef ta tr oo mt emperature in ac losed vessel. After two weeks, colourless blocks appeared and were separated by filtration. Experimental details The Ha tom sb onded to N2 was located in ad ifference ma pa nd refine dw ithout restraints. Other Ha toms were placed in calculated position sw it hC –H distance so f0 .9 3Aa nd were include di nt he refinement in the riding model approximaion with Uiso(H) =1 .2 Ueq(C). Discussion Pyridin-amines are interesting bridging ligands, as they contain two nitrogen coordination donor atoms, and an amine as ah ydrogen bond donor group [1]. The ligand pyridin-2-amine can easily bridge two metal ions [2]. With the presence of two donor atoms, the title compound might serve as ab uilding block in the formation of coordination polymers. Also, the title compound is an azahomotryptophane derivative known for pharmaceutical applications [3]. In order to expand the field, we here present the molecular structure of this compound. In the title crystal structure, the 3,5-dibromopyridin-2-amine molecule is nearly planar, with r.m.s. deviation of the pyridine heterocyclic non-hydrogen atoms is 0.022(2) Af or Br1 atom. In the crystal, molecules are arranged with two N–H···N hydrogen bond motifs, where the amine group serves as at wofold donor of the hydrogen atom sf or the two pyridin nitrogen atoms. The intermolecular N–H··· Nh ydrogen bond results in the formation of ad ime rw ith an R 2 2(8) graph-set motif [4]. There is also exist one weak intramolecular N2–H2A···Br1 interactions, which they may be effective in the stabilization of the structure.