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After cardiopulmonary bypass (CPB), the occurrence of systemic inflammatory response is often accompanied by a persistent compensatory anti-inflammatory response syndrome that can lead to a compromised immune competence termed immunoparalysis, rendering the patients susceptible to infections which is a leading complication following cardiac surgery. However, the underlying mechanisms of CPB-elicited immunoparalysis remain obscure. In this study we showed that peroxiredoxin 1 (Prdx1), a putative cytosolic antioxidant, was released immediately after CPB in a cohort of pediatric patients receiving congenital cardiac surgery. This increased Prdx1 was correlated to a reduced human leukocyte antigen-DR expression and an elevated interleukin-10 (IL-10) production, as well as a hypo-responsiveness of macrophages to endotoxin and a higher incidence of nosocomial infection. We demonstrated that substitution of Ser83 for Cys83 prevented Prdx1 from oligomerization and subsequent binding and internalization to macrophages. These effects mitigated Prdx1-induced IL-10 induction and endotoxin tolerance. Furthermore, after engagement with toll-like receptor (TLR) 4, clathrin-dependent endocytosis is crucial for Prdx1 to elicit IL-10 production in phagocytes. Congruently, inhibition of Prdx1/TLR4 endocytosis in phagocytes reversed the Prdx1/IL-10-mediated hypo-responsiveness to endotoxin. Our findings unveiled the possible mechanisms by which Prdx1 undertakes to cause immunoparalysis, and targeting endocytosis of Prdx1 could be a novel therapeutic approach for postoperative infections associated with CPB., Graphical abstract Image 1, Highlights • Cardiopulmonary bypass-elicited ischemia/reperfusion injury causes release of Prdx1. • High molecular weight forms of Prdx1 interact with TLR4 to initiate sterile inflammation. • Endocytosis of Prdx1/TLR4 induces IL-10 production that leads to immunoparalysis and subsequent septic inflammation. • Inhibition of Prdx1/TLR4 endocytosis reverses Prdx1/IL-10-mediated hypo-responsiveness to endotoxin in phagocytes.

Patients diagnosed with acute respiratory distress syndrome are generally severely distressed and associated with high morbidity and mortality despite aggressive treatments such as extracorporeal membrane oxygenation (ECMO) support. To identify potential biomarker of predicting value for appropriate use of this intensive care resource, plasma interleukin-10 along with relevant inflammatory cytokines and immune cell populations were examined during the early and subsequent disease courses of 51 critically ill patients who received ECMO support. High interleukin-10 levels at the time of ECMO installation and during the first 6 hours after ECMO support of these patients stand as a promising biomarker associated with grave prognosis. The initial interleukin-10 level is correlated to other conventional risk evaluation scores as a predictive factor for survival, and furthermore, elevated interleukin-10 levels are also related to a delayed recovery of certain immune cell populations such as CD14+CD16+, CD14+TLR4+ monocytes, and T regulator cells. Genetically, high interleukin-10 is associated to two polymorphic nucleotides (−592 C and −819 C) at the interleukin-10 gene promoter area. Our finding provides prognostic and mechanistic information on the outcome of severely respiratory distressed patients, and potentially paves the strategy to develop new therapeutic modality based on the principles of precision medicine.

Background This study was undertaken to investigate alterations of group II phospholipase A 2 (PLA 2 ) gene expression and its underlying mechanism in rat heart during different phases of sepsis. Materials and methods Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups, control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. PLA 2 enzyme activity, group II PLA 2 protein level, messenger RNA (mRNA) abundance, transcription rate, and half-life were measured. Results PLA 2 activity was decreased by 29% during early sepsis but it was increased by 49% during late sepsis. Group II PLA 2 protein level was decreased by 27% during early sepsis but it was increased by 35.3% during late sepsis. Group II PLA 2 mRNA was decreased by 21% during early sepsis but it was increased by 141% during late sepsis. The transcription rate of group II PLA 2 mRNA was reduced by 25% during early sepsis but it was elevated by 67% during late sepsis. The half-life of group II PLA 2 mRNA remained unaltered during early and late phases of sepsis. Conclusions These results demonstrate that PLA 2 activity, group II PLA 2 protein level, the mRNA abundance, and transcription rate were concurrently underexpressed during early sepsis, while they were overexpressed during late sepsis, with no change in the degradation of gene transcript. These data indicate that the biphasic changes in group II PLA 2 gene expression are regulated transcriptionally during sepsis.

Additional file 4: Figure S4. High initial Peroxiredoxin 1 level in cardiogenic shock patients who received ECMO support was associated with a poorer event-free survival. Kaplanâ Meier survival analysis of 7- and 30-day event free survivals in cardiogenic shock patients categorized by the cut-off values, as presented in Table 2. Event free survivals: survival status without multiple organ failure under the condition when assessment of sequential organ failure assessment (SOFA) score was lower than 15.

Phospholipase A(2) has been implicated to play a pivotal role in the pathogenesis of sepsis syndrome. The two major forms of phospholipase A(2) isoenzymes, secretory phospholipase A(2) and cytosolic phospholipase A(2), are overexpressed during sepsis. The objective of this study was to test the hypothesis that inhibition of the overexpressed secretory phospholipase A(2) and cytosolic phospholipase A(2) during sepsis benefits the disease's eventual outcome.Short-chain antisense oligonucleotide molecules were designed with the aid of computer software programs, and their in vitro efficacies were assessed in cell culture systems based on inhibition of target protein expression. The in vivo efficacies were determined in intact sepsis rats using 35-day survival rate as a primary efficacy end point.Animal research laboratory at a university.Male Sprague-Dawley rats (180-200 g).Sepsis was induced by cecal ligation and puncture. Antibiotics were administered subcutaneously once daily at 12 mg/kg, for 20 days. Oligonucleotides (antisense or mismatch) were administered intravenously once daily at 2 mg/kg to 0.8 mg/kg in a decreasing order, for 20 days.In cell culture systems, 21 of the 105 antisense constructs were found to be efficacious in inhibiting secretory phospholipase A(2) IIa and cytosolic phospholipase A(2) IVa protein expression. In sepsis rats, antisense oligonucleotides were capable of reducing their target protein expression by 18%-61% in major organs such as liver, heart, and kidney. In animal experiments, sepsis without any treatment (Group 1) had a median survival time of 2 days and a zero (0) percent survival rate at day 14. Sepsis with antibiotic treatment (Group 2) had a median survival time of 6 days and a 35-day survival rate of 28%. Sepsis with cotreatment of antibiotics and antisense oligonucleotides (one against secretory phospholipase A2 IIa and the other against cytosolic phospholipase A(2) IVa) (Group 4) increased the median survival time from 6 to 35 days and the 35-day survival rate from 28% to 58.8% as compared with antibiotics alone (Group 4 vs. Group 2; p.05). Sepsis with cotreatment of antibiotics and mismatch oligonucleotides (Group 3) did not affect the median survival time and the 35-day survival rate as compared to antibiotics alone (Group 3 vs. Group 2; p.05).The results demonstrate that antisense strategy against secretory phospholipase A(2) IIa and cytosolic phospholipase A(2) IVa can inhibit their target protein expression in major organs and greatly improve the clinical outcome, i.e., an absolute reduction in 35-day mortality of 30.8%, in rats with sepsis. Our studies, thus, provide an improved method for the treatment of sepsis by targeting multiple forms of phospholipase A(2) isoenzymes with DNA antisense oligomers.

As speech compression technologies have advanced, digital recording devices have become increasingly popular. However, data formats used in popular speech codecs are known a priori, such that compressed data can be modified easily via insertion, deletion, and replacement. This work proposes a content-dependent watermarking scheme suitable for codebook-excited linear prediction (CELP)-based speech codec that ensures the integrity of compressed speech data. Speech data are initially partitioned into many groups, each of which includes multiple speech frames. The watermark embedded in each frame is then generated according to the line spectrum frequency (LSF) feature in the current frame, the pitch extracted from the succeeding frame, the watermark embedded in the preceding frame, and the group index which is determined by the location of the current frame. Finally, some of the least significant bits (LSBs) of the indices indicating the excitation pulse positions or excitation vectors are substituted for the watermark. Conventional watermarking schemes can only detect whether compressed speech data are intact. They cannot determine where compressed speech data are altered by insertion, deletion, or replacement, whereas the proposed scheme can. Experiments established that the proposed scheme used in the G.723.1 6.3 kb/s speech codecs embeds 12 bits in each compressed speech frame with 189 bits, and only decreases the perceptual evaluation of speech quality (PESQ) by 0.11. Additionally, its accuracy in detecting the locations of attacked frames is very high, with only two normal frames mistaken as attacked frames. Therefore, the proposed watermarking scheme effectively ensures the integrity of compressed speech data.

The involvement of Na + , K + , Cl - or Ca 2 + in the regulation of salinity stress-induced proline accumulation via the inhibition of the activity of proline dehydrogenase (PDH; EC 1.4.3.1), a catabolic enzyme of proline, was investigated in the marine green macroalga Ulva fasciata Delile. After 6 h of exposure to elevated artificial seawater (ASW) salinity, adjusted either by increasing the NaCI content in 30‰ ASW (a change in ion ratio) or by concentrating ASW (a constant ion ratio), the contents of Na + , K + and Cl - linearly accumulated with increasing salinity from 30-90‰ (parts per thousand); the accumulation pattern of each ion was similar between the two treatments. An increase in NaCI content in ASW induced proline accumulation, but decreased both the PDH activity and the total and water-soluble Ca 2+ contents, while concentrated ASW had no effect. As compared to a constant value at 30‰, both the contents of total and water-soluble Ca 2 + and the activity of PDH decreased 1 h after exposure to 60‰ (adjusted by increasing NaCI content in 30‰ ASW) and concomitantly the content of seawater Ca 2+ increased, while proline accumulated after 3 h. The addition of 15 mM ethylene glycol-bis-(2-aminoethyl ether) N,N,N'-tetraacetic acid (EGTA) in 60‰ ASW (adjusted by increasing the NaCI content in 30‰ ASW) enhanced both the proline accumulation and the decrease in the content of total and water-soluble cellular Ca 2+ and the activity of PDH; the effects of EGTA were reversed by 10 mM CaCl 2 or 10 mM CaSO 4 , These results indicate that a loss of cellular Ca 2+ is associated with the NaCI induction of proline accumulation via an inhibition of PDH activity in U. fasciata.

Background The present study was undertaken to test hypothesis that altered transcription of secretory Phospholipase A2 (sPLA2) gene in rat liver is regulated by CCAAT/enhancer binding protein δ (C/EBPδ), and to assess its relationship to hepatic gluconeogenesis during the progression of sepsis. Methods Sepsis was induced by Cecal Ligation and Puncture (CLP). Experiments were divided into three groups, control, early sepsis (9 h after CLP), and late sepsis (18 h after CLP). Results DNA mobility and super shift assays reveal that C/EBP complexes in the liver consisted of at least three isoforms: C/EBPα, C/EBPβ, and C/EBPδ; and various C/EBP isoforms were capable of interacting with each other. Hepatocyte transfection experiments demonstrate that under normal conditions, binding of C/EBPδ to sPLA2 gene enhanced sPLA2 promoter activity and the binding resulted in an increase in hepatic gluconeogenesis. Under pathological conditions such as sepsis, binding of C/EBPδ to sPLA2 promoter increased during early and late phases of sepsis, and the increases in C/EBPδ binding correlated with increases in sPLA2 mRNA abundance and sPLA2 protein levels. Under otherwise the identical experimental conditions, hepatic gluconeogenesis was reduced during early and late phases of sepsis and the sepsis-induced reductions in liver gluconeogenesis were aggravated by binding of C/EBPδ to sPLA2 gene. Conclusions These results link C/EBPδ binding to altered sPLA2 promoter, and to hepatic gluconeogenesis under normal and pathological conditions. It is suggested that C/EBPδ-sPLA2- hepatic gluconeogenesis may function as a signalling axis affecting glucose homeostasis during the progression of sepsis.

In an attempt to build a good predictor of the performance of survey interviewers, we propose a feature selection method that derives the featuresi¦ strength (i.e., degree of usefulness) from various feature subsets drawn from a pool of all the features. The method also builds a predictor by using support vector regression (SVR) as the learning machine and the selected features as variables. Applying the method to a collection of 278 instances obtained from 67 interviewers par-ticipating in eight survey projects, we identified three critical features, experience and two attributional style variables, out of fifteen features. Compared with results of four existing methods, the proposed predictor produced the smallest predictive error. Furthermore, the three features utilized by our method were also identified as the most important features by the four compared methods.

To test the hypothesis that dexamethasone (Dex) treatment would restore rat hepatic bile acid coenzyme A-amino acid N-acyltransferase (rBAT) expression in septic rats after cecal ligation and puncture by increasing expression of retinoic acid X receptor alpha (RXRalpha), we assessed survival rate and bile and bile salt concentration in the Dex-treated septic group and compared these results with those for a nontreated septic group, a Dex-treated nonseptic group, and a sham group. Dexamethasone treatment (0.01 mg/kg) significantly improved the survival rate and increased the bile and bile salt concentration in the bile ducts of septic rats (P =0.05). In our assessment of bile salt-related genes, during sepsis, there were decreases in protein and mRNA expression of rBAT and cholesterol 7 alpha-hydroxylase (CYP7A1). Treatment with Dex restored expression of rBAT and RXR[alpha] but not CYP7A1, bile salt export pump, or multidrug resistance associated protein 2 (MRP2). Na+-taurocholate cotransport protein and organic anion transporting polypeptide 1 were unchanged. In addition, treatment with Dex also restored the DNA-binding activity of RXR/farnesoid-X receptor to rBAT promoter containing inverted repeat 1 sequence. In an experiment to confirm our findings, RXR[alpha] siRNA was found to significantly block Dex-induced increases in expression of rBAT in hepatocytes taken from septic rats (P0.01).Dex restored the expression of rBAT in septic rats by enhancing RXR[alpha], a process that might explain the mechanism underlying Dex's anticholestatic effect.

In H.264/AVC, many block types are employed to conduct inter and intra coding for determining the best one to achieve good coding efficiency. Accordingly, watermark data can be effectively embedded in these block types that are classified into three groups representing '1,' '0' and no datum. In inter coding, the block types of 16times16, 8times8 and 4times4 represent the watermark bit '1,' and the block types of 16 times 8, 8 times16, 8times4 and 4times8 denote the watermark bit '0.' In intra coding, the block type of 8 times 8 is the watermark bit '1,' and the block types of 16 times16 and 4times4 represent the watermark bit '0.' Other block types in inter and intra coding are treated as no datum. In the abovementioned grouping, the hierarchical and interleaving correlations of block types in the same and different groups, respectively, are adopted to minimize the performance distortion. Particularly, each frame is also pre-defined by a watermarking area to preserve coding performance and increase watermarking robustness. The computer simulations demonstrate that the proposed watermarking scheme can effectively hide data at a little increasing bit rate and almost no quality degradation.

With an overflow of multimedia information around us and an urgent need to identify data accurately, an audio and visual identification system with a high accuracy rate is developed to meet the demand. Classification and feature extraction are performed separately on audio and visual signals. Pending on the temporal correlation of the feature vectors of objects and speakers, indexes of all objects included in an audio/visual sequence are listed in a time sequence. In integrating the audio/visual features, every object or character of the key frames has a set of feature vectors; the user can select and search specific characters that have the audio and visual features from the entire index set. Due to integrating the audio/visual identification results in the time order, the proposed identification system can increase the accuracy about 4% and 6% in our experiments, comparing with the results using the audio features and visual features separately, respectively.

To detect where the speech waveform is replaced, inserted, or deleted, a content-based fragile watermark scheme is proposed. First, to make sure that the speech features used to generate the watermarks are not affected during the watermark embedding process, an approximated speech waveform is generated by setting some least significant bits (LSBs) being zero. Then speech features, LSP and pitch, are extracted from the approximated speech frame. The conventional watermark scheme in which the features are extracted only from a single frame where the watermarks are embedded is easily attacked and insufficient to detect where and how the speech is faked. Hence, in this work, features from multiple frames and other messages are combined together to generate the watermark. Finally, the watermarks and the synchronization code are embedded into the LSBs of specific speech signals. The theoretical analysis shows the proposed scheme is safe even if the cheater knows how it works. Therefore, the content-based fragile watermark scheme proposed herein can effectively protect the integrity of speech waveforms.

The wide use of digital speech recorders becomes a serious matter when they are involved in assisting with court rulings. How to distinguish if a recorded content is valid or not becomes a life-or-death question. In light of this concern, least significant bits (LSB) of excitation signals would be used as fragile watermarks in the hybrid speech vocoder. In addition, a location-variable content-dependent watermark generating mechanism is proposed. Such location-variable content-based watermark would allow users to detect where in the recording the content is being replaced, inserted, or deleted. Lastly, an attempt is done to store partial reconstruction data in the LSBs of excitation signals in the G.723.1 speech codec, so that the original speech content may be reconstructed after counterfeited. The proposed system is demonstrated to be a reliable system, with test results showing that a recording with watermarks has a perceptual evaluation of speech quality (PESQ) value down 0.2, while the accuracy in detecting faked regions can be up to 97.45%.

In this work, we propose the partial-correlation (PARCOR) coefficients scheme to model the cross areas of the several cylinders from the vocal tract. By using the relationship of the acoustic impedance proportional to the reciprocal of cross areas, the ratios of cross areas between each neighboring cylinders are used to model a speaker's vocal tract. The autoregressive model (AR model) is performed on the speech residual signals, that are produced from the inverse vocal tract transform based on the PARCOR, to generate features. These features with the conventional features from the Mel-Frequency Cepstral Coefficient (MFCC) are used for the identification engine of the Gaussian Mixture Model (GMM). According to our computer analyses in the TIMIT speech database, the proposed system can yield better identification performance than the conventional approach.

Changes in free proline concentrations following exposure to elevated NaCl in 35 psu artificial seawater (ASW) (an imbalance in ion ratio) or concentrated ASW (constant ion ratio) were investigated in the intertidal green alga Ulva fasciata Delile. When exposed to 55 psu achieved by adding NaCl to 35 psu ASW, free proline concentrations increased at hour 3 and reached a plateau after 12 h, whereas free proline concentrations in response to 55 psu achieved by concentrating ASW were constant during the treatment period. It is likely that an imbalance in ion ratio is a cue for the induction of a moderate accumulation of free proline in U. fasciata.

This paper examined the role of proline dehydrogenase (PDH; EC 1.4.3.1) in salinity-induced (adjusted by increasing NaCl contents in seawater) proline accumulation in the marine chlorophyte Ulva fasciata Delile, and also determined whether calmodulin modulates proline accumulation via a change in the activity and kinetic property of PDH. Upon exposure to varying salinity (30–120‰, that is, 317.9–1858 mМ NaCl in seawater) for 9 h, proline levels increased with increasing salinity, and were highly correlated with salinity (r2 = 0.97). In contrast, PDH-specific activity decreased with increasing salinity, and was inversely related with external salinity (r2 = 0.95) and proline levels (r2 = 0.80). When exposed to 60‰ salinity (831.3 mМ NaCl), PDH-specific activity decreased at hour 2, and proline levels increased at hour 3, as compared to the 35‰ (403.5 mМ NaCl) control. The addition of chlorpromazine (CP, 0.8 µМ) or trifluoperazine (TFP, 1 µМ), both calmodulin binding inhibitors, in seawater enhanced the increase in the levels of proline, but did not affect its Km value. It also enhanced the decrease in the specific activity and Vmax value of PDH in the 60‰-treated thallus discs. Overall, the reduction in catabolism via a decrease in PDH activity is associated with the NaCl-induced proline accumulation in U. fasciata, and the calmodulin-mediated signal transduction might be negatively involved in the regulation of proline accumulation via a modification in PDH properties.

Background Extracellular peroxiredoxin 1 (Prdx1) has been implicated to play a pivotal role in regulating inflammation; however, its function in tissue hypoxia-induced inflammation, such as severe cardiogenic shock patients, has not yet been defined. Thus, the objective of this study was to test the hypothesis that Prdx1 possesses prognostic value and instigates systemic inflammatory response syndrome in cardiogenic shock patients undergoing extracorporeal membrane oxygenation (ECMO) support. Methods We documented the early time course evolution of circulatory Prdx1, hypoxic marker carbonic anhydrase IX, inflammatory cytokines including IL-6, IL-8, IL-10, MCP-1, TNF-α, IL-1β, and danger signaling receptors (TLR4 and CD14) in a cohort of cardiogenic shock patients within 1 day after ECMO support. In vitro investigations employing cultured murine macrophage cell lines and human monocytes were applied to clarify the relationship between Prdx1 and inflammatory response. Results Prdx1 not only peaked earlier than all the other cytokines we studied during the initial course, but also predicted a worse outcome in patients who had higher initial Prdx1 plasma levels. The Prdx1 levels in patients positively correlated with hypoxic markers carbonic anhydrase IX and lactate, and inflammatory cytokines. In vitro study demonstrated that hypoxia/reoxygenation induced Prdx1 release from human monocytes and enhanced the responsiveness of the monocytes in Prdx1-induced cytokine secretions. Furthermore, functional inhibition by Prdx1 antibody implicated a crucial role of Prdx1 in hypoxia/reoxygenation-induced IL-6 secretion. Conclusions Prdx1 release during the early phase of ECMO support in cardiogenic shock patients is associated with the development of systemic inflammatory response syndrome and poor clinical outcomes. Thus, circulating Prdx1 provides not only prognostic information but may be a promising target against ischemia/reperfusion injury. Electronic supplementary material The online version of this article (doi:10.1186/s12967-016-0869-x) contains supplementary material, which is available to authorized users.