Aromadendrin protects mouse liver from sepsis-induced injury by inhibiting NF-κB signaling pathway

Purpose: To investigate the protective role of aromadendrin in septic liver injury in mice, and  its mechanism of action.Methods: Eight-week-old male C57BL/6 mice (n=6 for each group) were administrated with aromadendrin (SMB00175, Sigma-Aldrich) at 0 mg/kg, 30 mg/kg and 60 mg/kg via a hypodermic intraperitoneal injection. HE staining was used to examine liver histopathological structural changes in the liver while DAPI/Tunel staining was employed to evaluate liver cell apoptosis. The mRNA expression levels of TNF-α, IL-1β and IL-6 were determined by quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR). Moreover, enzyme-linked immunosorbent assay (ELISA)was applied to assess the levels of TNF-α, IL-1β and IL-6, as well as the activities of catalase (CAT), antioxidant glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, the protein levels of p65, p-p65, p-IκBα and IκBα were analyzed by Western blotting.Results: The liver tissues exhibited severe structural damages, with edema, necrosis, and neutrophil infiltration, but recovered as a result of aromadendrin treatment (p < 0.05). The increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in CLP mice were reduced by aromadendrin, which also attenuated liver injury and cell apoptosis. Aromadendrin inhibited the levels ofu TNF-α, IL-1β and IL-6 in the mice, while the activities of GSH and antioxidant enzymes (SOD and CAT) were also significantly lowered in the mice, but attenuated by aromadendrin (p < 0.05). Aromadendrin also prevented the increased level of MDA, and suppressed the phosphorylation of p65 and IκBα (p < 0.05).Conclusion: Aromadendrin protects mouse liver from sepsis-induced injury by inhibiting NF-κB signaling in vivo, thus suggesting a potential strategy for the therapy of sepsis-induced liver injury

Modeling the Conditional Heteroscedasticity and Leverage Effect in the Chinese Stock Markets

The Chinese stock market has experienced an astonishing growth and unprecedented development since its inception in the early 1990s, emerged to be the world\u27s second-largest by market value by the end of 2009. The Chinese stock market is also one of the most volatile markets, which has been called by many observers a “casino”. In the recent years there are several far-reaching events that have reshaped the Chinese stock markets. The most notable events include the “dot-com bubble” in 2000, China’s non-tradable shares reform in 2005 and the global financial crisis in 2008. It is noted that the “dot-com bubble” has caused the Chinese stock markets a sharp oscillation since 2000. With a short-lived bull, the Chinese stock markets experienced a nearly five years long bear market until June 2005 when the reform of non-tradable shares was implemented, which increased the liquidity and brought the markets back to a long-term bull run. Since the US sub-prime mortgage crisis the Chinese stock markets have shown extreme instability and severe volatility, which has become the major concern to the policy-makers and investors. Many existing studies have revealed that the financial time series data exhibit linear dependence in volatility, which indicates the presence of heteroskedasticity, implying the existence of volatility clustering. Although direct generalizations from the univariate GARCH models are straightforward, their applications are limited by practical issues associated with cumbersome computation and strong restrictions on parameters to guarantee positive definiteness of variance matrixes. This study intends to examine the presence of heteroskedasticity and the leverage effect in the two Chinese stock markets, and to capture the dynamics of conditional correlation between returns of China’s stock markets and those of the U.S. in a bivariate VCMGARCH framework. The results show that that the leverage effect is significant in both Shanghai and Shenzhen markets during the sample period in 2000-2008, and the conditional correlation between mainland China’s and the U.S. stock markets is quite low and highly volatile. The results indicate that that uncertainty derived from time-varying relationship between Shanghai and the U.S. stock markets is more significant than that between Shenzhen and the U.S. stock markets. In addition, the Chinese stock markets are found to be highly regimes persistent, thereby reducing potential benefits induced by actively trading. These findings have important implication for investors seeking opportunity of portfolio diversification

EFFECT OF THE Si POWDER ADDITIONS ON THE PROPERTIES OF SiC COMPOSITES

By means of transient plastic phase process, the SiC silicon carbide kiln furniture materials were produced through adding Si powder to SiC materials. At the condition of the same additions of SiO2 powder, the effect of the Si powder additions on properties of silicon carbide materials after sintered at 1450°C for 3 h in air atmosphere was studied by means of SEM and other analysis methods. The results showed that silicon powder contributes to both sintering by liquid state and plastic phase combination to improve the strength of samples. When the Si powder additions is lower than 3.5 %, the density and strength of samples increase and porosity decrease with increasing Si powder additions. However when the Si powder additions is higher than 3.5 %, the density and strength of samples decrease and porosity increase with increasing Si powder additions. With increasing of Si additions, the residual strength of sample after thermal shocked increased and linear change rate decreased, and get to boundary value when Si additions is 4.5 %. The results also indicated that at the same sintering temperature, the sample with 3.5 % silicon powder has maximum strength

PPARγ and PPARδ as Modulators of Neoplasia and Cell Fate

PPARγ and PPARδ agonists represent unique classes of drugs that act through their ability to modulate gene transcription associated with intermediary metabolism, differentiation, tumor suppression, and in some instances proliferation and cell adhesion. PPARγ agonists are used by millions of people each year to treat type 2 diabetes but may also find additional utility as relatively nontoxic potentiators of chemotherapy. PPARδ agonists produce complex actions as shown by their tumor promoting effects in rodents and their cholesterol-lowering action in dyslipidemias. There is now emerging evidence that PPARs regulate tumor suppressor genes and developmental pathways associated with transformation and cell fate determination. This review discusses the role of PPARγ and PPARδ agonists as modulators of these processes

GPUMemSort: A High Performance Graphics Co-processors Sorting Algorithm for Large Scale In-Memory Data

In this paper, we present a GPU-based sorting algorithm,GPUMemSort, which achieves high performance insorting large-scale in-memory data by take advantage ofGPU processors. It consists of two algorithms: an in-corealgorithm, which is responsible for sorting data in GPUglobal memory efficiently, and an out-of-core algorithm,which is responsible for dividing large-scale data intomultiple chunks that fit GPU global memory.GPUMemSort is implemented based on NVIDIA’s CUDAframework and some critical and detailed optimizationmethods are also presented. The tests of differentalgorithms have been run on multiple data sets. Theexperimental results show that our in-core sorting canoutperform other comparison-based algorithms andGPUMemSort is highly effective in sorting large-scale inmemorydata

Cooperative Fuzzy Games Approach to Setting Target Levels of ECs in Quality Function Deployment

Quality function deployment (QFD) can provide a means of translating customer requirements (CRs) into engineering characteristics (ECs) for each stage of product development and production. The main objective of QFD-based product planning is to determine the target levels of ECs for a new product or service. QFD is a breakthrough tool which can effectively reduce the gap between CRs and a new product/service. Even though there are conflicts among some ECs, the objective of developing new product is to maximize the overall customer satisfaction. Therefore, there may be room for cooperation among ECs. A cooperative game framework combined with fuzzy set theory is developed to determine the target levels of the ECs in QFD. The key to develop the model is the formulation of the bargaining function. In the proposed methodology, the players are viewed as the membership functions of ECs to formulate the bargaining function. The solution for the proposed model is Pareto-optimal. An illustrated example is cited to demonstrate the application and performance of the proposed approach

3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases

BACKGROUND: Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. METHODS: Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. RESULTS: Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. CONCLUSION: These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its importance in the metastatic process

A bibliometric analysis on discovering anti-quorum sensing agents against clinically relevant pathogens: current status, development, and future directions

BackgroundQuorum sensing is bacteria’s ability to communicate and regulate their behavior based on population density. Anti-quorum sensing agents (anti-QSA) is promising strategy to treat resistant infections, as well as reduce selective pressure that leads to antibiotic resistance of clinically relevant pathogens. This study analyzes the output, hotspots, and trends of research in the field of anti-QSA against clinically relevant pathogens.MethodsThe literature on anti-QSA from the Web of Science Core Collection database was retrieved and analyzed. Tools such as CiteSpace and Alluvial Generator were used to visualize and interpret the data.ResultsFrom 1998 to 2023, the number of publications related to anti-QAS research increased rapidly, with a total of 1,743 articles and reviews published in 558 journals. The United States was the largest contributor and the most influential country, with an H-index of 88, higher than other countries. Williams was the most productive author, and Hoiby N was the most cited author. Frontiers in Microbiology was the most prolific and the most cited journal. Burst detection indicated that the main frontier disciplines shifted from MICROBIOLOGY, CLINICAL, MOLECULAR BIOLOGY, and other biomedicine-related fields to FOOD, MATERIALS, NATURAL PRODUCTS, and MULTIDISCIPLINARY. In the whole research history, the strongest burst keyword was cystic-fibrosis patients, and the strongest burst reference was Lee and Zhang (2015). In the latest period (burst until 2023), the strongest burst keyword was silver nanoparticle, and the strongest burst reference was Whiteley et al. (2017). The co-citation network revealed that the most important interest and research direction was anti-biofilm/anti-virulence drug development, and timeline analysis suggested that this direction is also the most active. The key concepts alluvial flow visualization revealed seven terms with the longest time span and lasting until now, namely Escherichia coli, virulence, Pseudomonas aeruginosa, virulence factor, bacterial biofilm, gene expression, quorum sensing. Comprehensive analysis shows that nanomaterials, marine natural products, and artificial intelligence (AI) may become hotspots in the future.ConclusionThis bibliometric study reveals the current status and trends of anti-QSA research and may assist researchers in identifying hot topics and exploring new research directions

Inflammatory Markers of the Systemic Capillary Leak Syndrome (Clarkson Disease)

Objectives: The Systemic Capillary Leak Syndrome (SCLS) is a rare and potentially fatal disorder resembling systemic anaphylaxis that is characterized by transient episodes of hypotensive shock and peripheral edema. The pathogenesis of SCLS is unknown, and triggers for attacks are apparent only in a minority of patients. We introduce a clinical algorithm for the diagnosis of SCLS, and we investigated potential serum biomarkers of acute SCLS episodes. Methods: We analyzed serum cytokines in a cohort of 35 patients with an established diagnosis of SCLS and characterized the effects of SCLS sera on endothelial cell function. We investigated the cellular source(s) of CXCL10, a chemokine that was significantly elevated in both basal and acute SCLS sera, by flow cytometry. Results: Several cytokines were elevated in acute SCLS sera compared to baseline or sera from healthy controls, including CXCL10, CCL2, IL-1β, IL-6, IL-8, IL-12 and TNFα. The majority of acute sera failed to activate endothelial cells as assessed by surface adhesion marker expression. Monocytes appear to be the major source of serum CXCL10, and the percentage of CXLC10+ monocytes in response to IFNγ stimulation was increased in SCLS subjects compared to controls. Conclusions: The presence of proinflammatory cytokines in acute SCLS sera suggests that inflammation or infection may have a role in triggering episodes. The enhanced capacity of monocytes from SCLS patients to produce CXCL10 suggests a new therapeutic avenue for SCLS