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Background: Mitochondrial DNA (mtDNA) was reported as a pro-inflammatory agent. In our previous study, elevation of plasma mtDNA was revealed after cardiac surgery with cardiopulmonary bypass (CPB). Platelets were activated during the cardiac surgery and recent study revealed its ability to release mtDNA. Our present study postulated that the elevated plasma mtDNA comes from activated platelets, which plays a critical role in post-CPB inflammatory responses.Methods: Sixty-eight patients who underwent coronary artery bypass graft (CABG) with CPB were enrolled in our study. Blood samples were collected before induction of anaesthesia (T1), at the end of CPB (T2), 12 h post-CPB (T3), 24 h post-CPB (T4), 48 h post-CPB (T5) and 72 h post-CPB (T6). Blood samples were analyzed for the routine blood test and prepared for plasma isolation. MtDNA concentration was measured by rt-PCR, and TNF-α and IL-6 were examined by specific ELISA kits. Subgroup study was analyzed by activation levels of platelet. Basic information, mtDNA level, TNF-α level and IL-6 level were all carefully studied in each quartile.Results: Activation level of platelets increased and peaked at T2, which decreased gradually from T3 to T6 (P < 0.05). MtDNA increased after CPB, peaked at T3, and then backed from T4 to T6 (P < 0.05). Bivariate correlation between peak activation level of platelets and peak plasma mtDNA level showed a positive correlation between these two parameters (r = 0.683, P < 0.0001). Both TNF-α and IL-6 showed similar patterns as mtDNA, with an increase from T1 to T3 and a decrease from T4 to T6 (P < 0.05). Subgroup analysis further demonstrated that patients with higher activation levels of PLT had higher plasma mtDNA levels and inflammatory level (P < 0.05).Conclusions: Our study revealed the dynamic changes of activation level of platelets and identified the interesting association between platelets activation and plasma mtDNA, suggesting a novel potential mechanism of activated platelets-induced post-CPB inflammatory responses. [ABSTRACT FROM AUTHOR]

Anlotinib-mediated angiogenic remodeling was delineated in various tumors. Meanwhile, we previously showed that anlotinib inhibited tumor angiogenesis in anaplastic thyroid cancer (ATC). However, the potential role of anlotinib on cell lethality in ATC remains an enigma. Herein, we found that anlotinib inhibited the viability, proliferation, and migration of KHM-5M, C643, and 8505C cells in a dose-dependently manner. Under anlotinib treatment, PANoptosis (pyroptosis, apoptosis, and necroptosis) markers were not changed; however, ferroptosis targets (transferrin, HO-1, FTH1, FTL, and GPX4) were significantly downregulated. ROS levels also increased in a concentration-dependent manner after anlotinib treatment in KHM-5M, C643, and 8505C cells. In addition, protective autophagy was activated in response to anlotinib, and autophagic blockade potentiated anlotinib-mediated ferroptosis and antitumor effects in vitro and in vivo. Our new discovery identified autophagy-ferroptosis signaling pathway which provides mechanistic insight into anlotinib-mediated cell death, and synergistic combination therapy may help develop new ATC treatment strategies. [ABSTRACT FROM AUTHOR]

Backgroud: Cardiac surgery with cardiopulmonary bypass (CPB) may cause inflammatory responses, which can deteriorate the outcomes. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6,-8 and -10, can act as both the effector and the predictor for post-operative inflammatory responses. Plasma mitochondrial DNA (mtDNA) was found as a pro-inflammatory agent recently, which was released when cells were insulted. Methods: In the present study, we included 38 patients undergoing coronary artery bypass graft (CABG) to analyze their perioperative plasma mtDNA and levels of inflammatory cytokines. Blood samples were collected before aortic cross-clamping (T1), at the end of CPB (T2), 6 h post-CPB (T3), 12 h post-CPB (T4), and 24 h post-CPB (T5). Rt-PCR and specific ELISA kits were used to quantify the plasma mtDNA and inflammatory cytokines, respectively. Bivariate correlations analysis was used to check the correlations between plasma mtDNA and inflammatory cytokines respectively. Results: Results shown that plasma mtDNA elevated significantly at T2 and peaked at T4. Furthermore,plasma TNF-α, IL-6 and IL-8 levels significantly increased at T2 and peaked at T3 while IL-10 elevated and peaked at T2. Bivariate correlations analysis showed that the peak plasma mtDNA were positively correlated with the peak TNF-α (r = 0.677, P < 0.001), the peak IL-6 (r = 0.706, P < 0.001), the peak IL-8 (r = 0.584, P < 0.001) and the peak IL-10 (r = 0.565, P < 0.001). Conclusion: We found that plasma mtDNA might play a key role in CPB-induced post-operative inflammatory responses. [ABSTRACT FROM AUTHOR]

Cisplatin and its analogues are first-line chemotherapeutic agents for the treatment of numerous human cancers. A major inconvenience in their clinical use is their strong tendency to link to sulfur compounds, especially in kidney, ultimately leading to severe nephrotoxicity. To overcome this drawback we prepared a variety of platinum complexes with sulfur ligands and analyzed their biological profiles. Here, a series of six platinum(II) compounds bearing a conserved O,S binding moiety have been synthesized and characterized as experimental anticancer agents. The six compounds differ in the nature of the O,S bidentate β-hydroxydithiocinnamic alkyl ester ligand where both the substituents on the aromatic ring and the length of the alkyl chain may be varied. The two remaining coordination positions at the square-planar platinum(II) center are occupied by a chloride ion and a DMSO molecule. These novel platinum compounds showed an acceptable solubility profile in mixed DMSO-buffer solutions and an appreciable stability at physiological pH as judged from analysis of their time-course UV-visible absorption spectra. Their anti-proliferative and pro-apoptotic activities were tested against the cisplatin-resistant lung cancer cell line A549. Assays revealed significant effects of the sample drugs at low concentrations (in the μmolar range); initial structure-activity-relationships are proposed. The activity of the apoptosis-promoting protein caspase 3/7 was determined; results proved that these novel platinum compounds, under the chosen experimental conditions, preferentially induce apoptosis over necrosis. Reactions with the model proteins cytochrome c, lysozyme and albumin were studied by ESI MS and ICP-OES to gain preliminary mechanistic information. The tested compounds turned out to metalate the mentioned proteins to a large extent. In view of the obtained results these novel platinum complexes qualify themselves as promising cytotoxic agents and merit, in our opinion, a deeper pharmacological evaluation as prospective anticancer agents. [ABSTRACT FROM AUTHOR]

This paper proposes a novel wireless sensor network (WSN) localization algorithm. Accurate localization is the key technology of WSN. From various aspects many scholars consider localization problem, which is more effective to regard WSN localization problem as an optimization problem. Plant growth simulation algorithm (PGSA) is a kind of new intelligent optimization algorithm, which is intelligent simulation of plant growth in nature way. In addition to the common characteristics of intelligent algorithms, PGSA could be good robustness and guarantee the global optimal solution, etc. In this paper, further enhances the algorithm by adding the plant root of adaptive backlight function to effectively improve the computing speed and localization precision. Comparing this algorithm with simulated annealing algorithm (SAA), simulation results show that this algorithm has a higher and more consistent localization precision and faster computing speed. [ABSTRACT FROM AUTHOR]

The steam generator tube rupture (SGTR) accident is one of the design basis accidents of lead-cooled fast reactor (LFR). In the event of such an accident, a subcooled water jet is generated in the lead pool of primary circuit, which forms a complicated distribution of the liquid metal-gas two-phase flow. The detection of the two-phase interface and migration of steam bubbles is an significant part of reactor safety analysis. Due to the opacity, corrosiveness, high temperature of liquid metal, and the current limitations of measurement methods involving liquid metal-gas two-phase flow, a diamond-like carbon (DLC) coated wire-mesh sensor (WMS) based on electrical principles was proposed in this paper. The sensor could achieve the image of the liquid metal-gas two-phase distribution inside the flow channel, while preventing the corrosion failure of the sensor. Based on the COMSOL software, a numerical model of the DLC coated WMS was established. Selecting the materials of two phases as liquid GaInSn alloy and air, the simulation of the electric field in the liquid metal environment containing a single bubble was performed, and an electric signal value matrix representing the liquid metal-gas two-phase was output. The signal matrix was further normalized through the linear relation to obtain the two-phase distribution image, which verified the application feasibility of the coated WMS in liquid metal. In addition, a prototype of the DLC coated WMS was manufactured, and the numerical simulation results were experimentally validated in order to demonstrate the rationality of the numerical model. Furthermore, the influence of different structural parameters on the measurement accuracy of coated WMS was studied in detail by changing the transverse interval, axial interval, electrode diameter, coat thickness, and the size of air bubble. The simulation results show that the electric field distribution in the liquid metal-gas two-phase environment differs significantly from that in conventional fluid medias such as water-gas due to the high relative permittivity of liquid metal. On the other hand, considering the resolution of the WMS and the phenomenon of electric signal crosstalk, the transverse interval of electrode should be selected between 2-3 mm, and the axial interval should be selected between 1.5-2 mm to achieve high measurement accuracy. The coat thickness and electrode diameter have little influence on the measurement accuracy, but to reduce the intrusion effect of the WMS, the electrode diameter should be selected between 0.4-0.5 mm and the coat thickness should not exceed half of the electrode radius. This study could guide the practical application of DLC coated WMS in the liquid metal-gas two-phase environment and provide a technical basis for the analysis of multi-phase distribution under SGTR accidents.

Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD+ depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD+ levels with NAD+ or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention. [ABSTRACT FROM AUTHOR]

Objective To determine the true community prevalence of human cystic (CE) and alveolar (AE) echinococcosis (hydatid disease) in a highly endemic region in Ningxia Hui, China, by detecting asymptomatic cases. Methods Using hospital records and ‘AE-risk’ landscape patterns we selected study communities predicted to be at risk of human echinococcosis in Guyuan, Longde and Xiji counties. We conducted community surveys of 4773 individuals from 26 villages in 2002 and 2003 using questionnaire analysis, ultrasound examination and serology. Findings Ultrasound and serology showed a range of prevalences for AE (0-8.1%; mean 2%) and CE (0-7.4%; mean 1.6%), with the highest prevalence in Xiji (2% for CE, 2.5% for AE). There were significant differences in the prevalence of CE, AE and total echinococcosis between the three counties and villages (with multiple degrees of freedom). While hospital records showed 96% of echinococcosis cases attributable to CE, our survey showed a higher prevalence of human AE (56%) compared to CE (44%). Questionnaire analysis revealed that key risk factors for infection were age and dog ownership for both CE and AE, and Hui ethnicity and being female for AE. Drinking well-water decreased the risk for both AE and CE. Conclusions Echinococcosis continues to be a severe public health problem in this part of China because of unhygienic practices/ habits and poor knowledge among the communities regarding this disease. [ABSTRACT FROM AUTHOR]