731 research outputs found
The potential application of ultra-nanocrystalline diamond films for heavy ion irradiation detection
[[abstract]]The potential of utilizing the ultra-nanocrystalline (UNCD) films for detecting the Au-ion irradiation was investigated. When the fluence for Au-ion irradiation is lower than the critical value (fc = 5.0 Ă 1012 ions/cm2) the turn-on field for electron field emission (EFE) process of the UNCD films decreased systematically with the increase in fluence that is correlated with the increase in sp2-bonded phase (Ï*-band in EELS) due to the Au-ion irradiation. The EFE properties changed irregularly, when the fluence for Au-ion irradiation exceeds this critical value. The transmission electron microscopic microstructural examinations, in conjunction with EELS spectroscopic studies, reveal that the structural change preferentially occurred in the diamond-to-Si interface for the samples experienced over critical fluence of Au-ion irradiation, viz. the crystalline SiC phase was induced in the interfacial region and the thickness of the interface decreased. These observations implied that the UNCD films could be used as irradiation detectors when the fluence for Au-ion irradiation does not exceed such a critical value.[[incitationindex]]SCI[[booktype]]é»ć
The 3D-tomography of the nano-clusters formed by Fe-coating and annealing of diamond films for enhancing their surface electron field emitters
[[abstract]]The Fe-coating and H2-annealed processes markedly increased the conductivity and enhanced the surface electron field emission (s-EFE) properties for the diamondfilms. The enhancement on the s-EFE properties for the diamondfilms is presumably owing to the formation of nano-graphite clusters on the surface of the films via the Fe-to-diamond interaction. However, the extent of enhancement varied with the granular structure of the diamondfilms. For the microcrystalline (MCD)films, the s-EFE process can be turned on at (E0)MCD = 1.9 V/ÎŒm, achieving a large s-EFE current density of (Je)MCD = 315 ÎŒA/cm2 at an applied field of 8.8 V/ÎŒm. These s-EFE properties are markedly better than those for Fe-coated/annealed ultrananocrystalline diamond(UNCD)films with (E0)UNCD = 2.0 V/ÎŒm and (Je)UNCD = 120 ÎŒA/cm2. The transmission electron microscopy showed that the nano-graphite clusters formed an interconnected network for MCDfilms that facilitated the electron transport more markedly, as compared with the isolated nano-graphitic clusters formed at the surface of the UNCDfilms. Therefore, the Fe-coating/annealing processes improved the s-EFE properties for the MCDfilms more markedly than that for the UNCDfilms. The understanding on the distribution of the nano-clusters is of critical importance in elucidating the authentic factor that influences the s-EFE properties of the diamondfilms. Such an understanding is possible only through the 3D-tomographic investigations.[[journaltype]]ćć€[[ispeerreviewed]]Y[[booktype]]é»ćç[[countrycodes]]US
Intraoperative hyperthermic intraperitoneal chemotherapy as adjuvant chemotherapy for advanced gastric cancer patients with serosal invasion
AbstractBackgroundTo evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) as an adjuvant chemotherapy in advanced gastric cancer (AGC) patients with serosal invasion.MethodsPatients who received radical surgery and palliative surgery between January 2002 and December 2010 were retrospectively examined. Patients were divided into two groups, namely, one group that underwent surgery and another group that underwent surgery with HIPEC. All patients who received HIPEC had suspected serosal invasion on an abdominal computed tomography or by the surgeon's assessment during the operation.ResultsThe prophylactic groups included 83 patients who underwent gastrectomy alone. A total of 29 patients underwent gastrectomy with HIPEC. The 5-year survival rates were 10.7% and 43.9%, respectively. The 5-year mean survival times were 22.66 (17.55â25.78) and 34.81 (24.97â44.66) months (p = 0.029), respectively. There were 52 patients who had a recurrence of carcinomatosis among 133 patients who had resections (52/133, 39.1%). The 3-year disease-free survival rate for carcinomatosis was 28.87% in the group that received surgery alone, whereas it was 66.03% in the group that received HIPEC. There was no significant difference in the rate of complication between the two groups in the prophylactic group (p = 0.542). Thus, curative surgery with HIPEC had a better prognosis for AGC with serosal invasion. The carcinomatosis recurrence time was longer in patients who underwent gastrectomy with HIPEC and received R0 resection.ConclusionThe survival benefit of HIPEC as an adjuvant therapy for gastric cancer patients with serosal invasion should be validated in a large cohort
Mitochondrial oxidative phosphorylation complex regulates NLRP3 inflammasome activation and predicts patient survival in nasopharyngeal carcinoma
© 2020 Chung et al. We previously reported that tumor inflammasomes play a key role in tumor control and act as favorable prognostic markers in nasopharyngeal carcinoma (NPC). Activated inflammasomes frequently form distinguishable specks and govern the cellular secretion of IL-1ÎČ. However, we know little about the biological and biochemical differences between cells with and without apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) speck formation. In this study, we used proteomic iTRAQ analysis to analyze the proteomes of NPC cells that differ in their ASC speck formation upon cisplatin treatment. We identified proteins that were differentially over-expressed in cells with specks, and found that they fell into two Gene ontology (GO) pathways: mitochondrial oxidative phosphorylation (OxPhos) and ubiquinone metabolism. We observed up-regulation of various components of the OxPhos machinery (including NDUFB3, NDUFB8 and ATP5B), and subsequently found that these changes lead to mitochondrial ROS (mtROS) production, which promotes the formation and activation of NLRP3 inflammasomes and subsequent pyroptosis. In NPC patients, better local recurrence-free survival was significantly associated with high-level expression of NDUFB8 (p = 0.037) and ATP5B (p = 0.029), as examined using immunohistochemistry. However, there were no significant associations between the expression of NDUFB8 and ATP5B with overall survival of NPC patients. Together, our results demonstrate that up-regulated mitochondrial OxPhos components are strongly associated with NLRP3 inflammasome activation in NPC. Our findings further suggest that high-level expression of OxPhos components could be markers for local recurrence and/or promising therapeutic targets in patients with NPC
Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation.
Activation of the NLRP3 inflammasome is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Pyk2 is essential for NLRP3 inflammasome activation. Here we show that the Src-family kinases (SFKs)-Cbl axis plays a pivotal role in suppressing NLRP3 inflammasome activation in response to stimulation by nigericin or ATP, as assessed using gene knockout and gene knockdown cells, dominant active/negative mutants, and pharmacological inhibition. We reveal that the phosphorylation of Cbl is regulated by SFKs, and that phosphorylation of Cbl at Tyr371 suppresses NLRP3 inflammasome activation. Mechanistically, Cbl decreases the level of phosphorylated Pyk2 (p-Pyk2) through ubiquitination-mediated proteasomal degradation and reduces mitochondrial ROS (mtROS) production by contributing to the maintenance of mitochondrial size. The lower levels of p-Pyk2 and mtROS dampen NLRP3 inflammasome activation. In vivo, inhibition of Cbl with an analgesic drug, hydrocotarnine, increases inflammasome-mediated IL-18 secretion in the colon, and protects mice from dextran sulphate sodium-induced colitis. Together, our novel findings provide new insights into the role of the SFK-Cbl axis in suppressing NLRP3 inflammasome activation and identify a novel clinical utility of hydrocortanine for disease treatment
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Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis
The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1ÎČ secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, and only the phosphorylated ASC could participate in speck formation and trigger IL-1ÎČ secretion. Moreover, the clinical-trial-tested Pyk2/FAK dual inhibitor PF-562271 reduced monosodium urate-mediated peritonitis, a disease model used for studying the consequences of NLRP3 activation. Our results suggest that although Pyk2 and FAK are involved in inflammasome activation, only Pyk2 directly phosphorylates ASC and brings ASC into an oligomerization-competent state by allowing Tyr146 phosphorylation to participate ASC speck formation and subsequent NLRP3 inflammation
Equivalent efficacies of reverse hybrid and concomitant therapies in first- line treatment of Helicobacter pylori infection
Background and AimConcomitant therapy is a recommended first- line treatment for Helicobacter pylori infection in most national or international consensuses. Reverse hybrid therapy is a modified 14- day concomitant therapy without clarithromycin and metronidazole in the final 7ĂÂ days. This study aims to test whether 14- day reverse hybrid therapy is non- inferior to 14- day concomitant therapy in the first- line treatment of H.ĂÂ pylori infection.MethodsHelicobacter pylori- infected adult patients were randomly assigned to receive either reverse hybrid therapy (dexlansoprazole 60ĂÂ mg o.d. plus amoxicillin 1ĂÂ g b.d. for 14ĂÂ days, and clarithromycin 500ĂÂ mg plus metronidazole 500ĂÂ mg b.d. for initial 7ĂÂ days) or concomitant therapy (dexlansoprazole 60ĂÂ mg once o.d. plus amoxicillin 1ĂÂ g, clarithromycin 500ĂÂ mg, and metronidazole 500ĂÂ mg b.d. for 14ĂÂ days). H.ĂÂ pylori status was assessed 6ĂÂ weeks after the end of treatment.ResultsHelicobacter pylori- infected participants (nĂÂ =ĂÂ 248) were randomized to receive either 14- day reverse hybrid therapy (nĂÂ =ĂÂ 124) or 14- day concomitant therapy (nĂÂ =ĂÂ 124). Intention- to- treat analysis demonstrated that the two therapies had comparable eradication rate (95.2% vs 93.5%; 95% confidence interval, - 4.0% to 7.4%; PĂÂ =ĂÂ 0.582). However, reverse hybrid therapy had a much lower frequency of adverse events than concomitant therapy (20.2% vs 38.7%, PĂÂ =ĂÂ 0.001). The two therapies exhibited comparable drug adherence (93.5% vs 87.9%, PĂÂ =ĂÂ 0.125).ConclusionsFourteen- day reverse hybrid therapy and 14- day concomitant therapy are equivalent in efficacy for the first- line treatment of H.ĂÂ pylori infection. However, reverse hybrid therapy has fewer adverse events compared with concomitant therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163472/2/jgh15034_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163472/1/jgh15034.pd
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