Universal Platform for Robust Dual-Atom Doped 2D Catalysts with Superior Hydrogen Evolution in Wide pH Media.

Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2. First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.

HCMV-encoded viral protein US12 promotes autophagy by inducing autophagy flux.

The human cytomegalovirus (HCMV)-encoded US12 gene family is a group of ten predicted seven-transmembrane domain proteins that are structurally similar to G-protein-coupled receptors or transmembrane Bax inhibitor-1 motif-containing proteins; however, the roles of US12 family proteins in virus-host interactions remain to be discovered. Here, we suggest a new function of the US12 protein in regulating cellular autophagy. US12 is predominantly located to the lysosome and interacts with the lysosomal membrane protein 2 (LAMP2). A liquid chromatography-mass spectrometry (MS)/MS-based targeted proteomics analysis shows that US12 is tightly correlated with autophagy. US12 induces autophagy via upregulating ULK1 phosphorylation and subsequent LC3-II conversion, thereby accelerating autophagic flux. Moreover, HeLa cells overexpressing US12 displays intense LC3-specific staining and autolysosome formation even under nutrient-sufficient conditions. Furthermore, the physical interaction of p62/SQSTM1 with US12 is involved in the resistance to the degradation of p62/SQSTM1 by autophagy, despite the induction of both autolysosome formation and autophagic flux. Although the effect of US12 expression in HCMV infection on autophagy remains undetermined, these findings provide new insights into the viral drivers of host autophagy during HCMV evolution and pathogenesis.

Short-term Outcomes of Single-port Versus Multiport Laparoscopic Surgery for Colon Cancer: The SIMPLE Multicenter Randomized Clinical Trial.

OBJECTIVE: To compare short-term perioperative outcomes of single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for colon cancer. SUMMARY BACKGROUND DATA: Although many studies reported short- and long-term outcomes of SPLS for colon cancer compared with MPLS, few have reported results of randomized controlled trials. METHODS: This was a multicenter, prospective, randomized controlled trial with a noninferiority design. It was conducted between August 2011 and June 2017 at 7 sites in Korea. A total of 388 adults (aged 19-85 yrs) with clinical stage I, II, or III adenocarcinoma of the ascending or sigmoid colon were enrolled and randomized. The primary endpoint was 30-day postoperative complication rates. Secondary endpoints were the number of harvested lymph nodes, length of the resection margin, postoperative pain, and time to functional recovery (bowel movement and diet). Patients were followed for 30 days after surgery. RESULTS: Among 388 patients, 359 (92.5%) completed the study (SPLS, n = 179; MPLS, n = 180). The 30-day postoperative complication rate was 10.6% in the SPLS group and 13.9% in the MPLS group (95% confidence interval, -10.05 to 3.05 percentage points; P < 0.0001). Total incision length was shorter in the SPLS group than in the MPLS group (4.6 cm vs 7.2 cm, P < 0.001), whereas the length of the specimen extraction site did not differ (4.4 cm vs 4.6 cm, P = 0.249). There were no significant differences between groups for all secondary endpoints and all other outcomes. CONCLUSIONS: Even though there was no obvious benefit to SPLS over MPLS when performing colectomy for cancer, our data suggest that SPLS is noninferior to MPLS and can be considered an option in selected patients, when performed by experienced surgeons.Trial registration: ClinicalTrials.gov Identifier: NCT01480128.

Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial.

BACKGROUND: Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. METHODS: All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer's protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer's instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). DISCUSSION: This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. TRIAL REGISTRATION: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1 .

Three-dimensional double-echo steady-state with water excitation magnetic resonance imaging to localize the intraparotid facial nerve in patients with deep-seated parotid tumors.

PURPOSE: To assess the utility of three-dimensional double-echo steady-state with water excitation (3D-DESS-WE) imaging for localizing deep-seated parotid tumors in relation to the facial nerve. METHODS: A prospective study comparing the surgical outcomes of parotidectomy with or without 3D-DESS-WE sequence is currently enrolling the patients. Magnetic resonance imaging data from the first 25 patients with 3D-DESS-WE sequence were reviewed. Visibility of the intraparotid facial nerve was independently assessed by two neuroradiologists. The diagnostic performance of the 3D-DESS-WE sequence for prediction of deep lobe involvement was compared with that of two conventional methods based on the retromandibular vein line (RMVL) and facial nerve line (FNL). The relationship between the tumor and the main trunk of the facial nerve was also evaluated on the 3D-DESS-WE sequence. RESULTS: On 3D-DESS-WE images, the main trunk, temporofacial division, and cervicofacial division of the intraparotid facial nerve were visualized in 100% (25/25), 48% (12/25), and 36% (9/25) of patients, respectively. The diagnostic accuracy of the 3D-DESS-WE sequence for prediction of deep lobe involvement was 92% (23/25), which was significantly superior to that of the RMVL (68% [17/25]; p = 0.008) and FNL (64% [16/25]; p = 0.004) methods. The relationship between the tumor and the main trunk of the facial nerve was correctly predicted in 92% (23/25) of 3D-DESS-WE images. CONCLUSION: By direct visualization of the facial nerve, the 3D-DESS-WE sequence improved the preoperative localization of the intraparotid facial nerve in deep-seated parotid tumors. This information may help better surgical planning for deep-seated parotid tumors.

Quality of life and patient satisfaction after single- and multiport laparoscopic surgery in colon cancer: a multicentre randomised controlled trial (SIMPLE Trial).

BACKGROUND: The clinical benefits of single-port laparoscopic surgery (SPLS) in patients with colon cancer patients are unclear because only a few studies have reported on the quality of life (QoL) of such patients. This study aimed to compare the QoL and patient satisfaction between SPLS and multiport laparoscopic surgery (MPLS) in colon cancer. METHODS: The multicentre randomised controlled SIngle-port versus MultiPort Laparoscopic surgEry (SIMPLE) trial included patients with colon cancer who underwent radical surgery at seven hospitals in South Korea. We performed a pre-planned secondary analysis of the QoL data of 359 patients from that trial. The QoL was surveyed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 preoperatively and at 1, 3, 6, and 12 months postoperatively. Patient satisfaction was measured with a 5-point questionnaire at these postoperative time points. RESULTS: Overall, 145 and 147 patients were included in the SPLS and MPLS groups, respectively. Most QoL domains were similar between the groups. In the subgroup analysis of patients without adjuvant chemotherapy, patients in the SPLS group presented with significantly better global health status (p = 0.017), fatigue (p = 0.047), and pain (p = 0.005) scores and tended to have improved physical (p = 0.055), emotional (p = 0.064), and social (p = 0.081) functioning, with marginal significance at 1 month postoperatively, compared to those in the MPLS group. Patient satisfaction regarding surgery (p = 0.002) and appearance of the abdominal scar (p = 0.002) was significantly higher with SPLS than with MPLS at 12 months postoperatively. CONCLUSION: Patients who underwent SPLS without adjuvant chemotherapy had better global health status, fatigue status, and pain at 1 month postoperatively; however, these improvements were minimal and temporary. In the near future, the effect of SPLS on postoperative QoL should be confirmed through a randomised controlled trial targeting the QoL in colon cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01480128.

FAM83H and Nectin1 expression are related with survival and relapse of bladder urothelial carcinoma patients.

BACKGROUND: FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray. METHODS: We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression. RESULTS: Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients. CONCLUSIONS: Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients.

Radiologic findings and the molecular expression profile of diffuse midline glioma H3 K27M mutant.

BACKGROUND: Diffuse midline glioma H3 K27M-mutant (DMG) are reported to show heterogeneous radiologic imaging features in children. We hypothesized that other genetic mutations may contribute to this heterogeneity. PURPOSE: To describe the magnetic resonance imaging (MRI) findings of DMG in adult patients and to correlate the imaging findings with the molecular expression profile. MATERIAL AND METHODS: Eighteen patients with pathologically proven DMG were enrolled. On preoperative MRI, the following were evaluated: location; size of the lesion; ratio of non-enhancing (NE) and contrast-enhancing (CE) area; presence of cortical invasion and necrotic component; maximum relative cerebral blood volume ratio (rCBV ratio) of NE and CE portions; and minimum apparent diffusion coefficient (ADC) of NE and CE portions, among others. Molecular profiles including ATRX expression and p53 mutation were reviewed to find correlation with imaging features. RESULTS: Thalamus was the most commonly involved location, followed by pons and tectum. Five patients showed loss of normal ATRX expression. p53 mutation was positive in 12 patients. 40% of normal ATRX expression patients had cortical involvement and 20% had leptomeningeal seeding; none of the patients with ATRX loss had cortical involvement or leptomeningeal seeding. Patients with normal ATRX expression showed significantly higher rCBV ratio and lower ADC value in the NE area than patients with ATRX loss (P=0.04, 0.016). p53 mutation status did not correlate with any imaging finding. CONCLUSION: Cortical invasion, leptomeningeal tumor spread, lower ADC value and higher rCBV ratio in NE areas of DMG may be related to normal expression of ATRX.

A Fully Automated Analytic System for Measuring Endolymphatic Hydrops Ratios in Patients With Ménière Disease via Magnetic Resonance Imaging: Deep Learning Model Development Study.

BACKGROUND: Recently, the analysis of endolymphatic hydropses (EHs) via inner ear magnetic resonance imaging (MRI) for patients with Ménière disease has been attempted in various studies. In addition, artificial intelligence has rapidly been incorporated into the medical field. In our previous studies, an automated algorithm for EH analysis was developed by using a convolutional neural network. However, several limitations existed, and further studies were conducted to compensate for these limitations. OBJECTIVE: The aim of this study is to develop a fully automated analytic system for measuring EH ratios that enhances EH analysis accuracy and clinical usability when studying Ménière disease via MRI. METHODS: We proposed the 3into3Inception and 3intoUNet networks. Their network architectures were based on those of the Inception-v3 and U-Net networks, respectively. The developed networks were trained for inner ear segmentation by using the magnetic resonance images of 124 people and were embedded in a new, automated EH analysis system-inner-ear hydrops estimation via artificial intelligence (INHEARIT)-version 2 (INHEARIT-v2). After fivefold cross-validation, an additional test was performed by using 60 new, unseen magnetic resonance images to evaluate the performance of our system. The INHEARIT-v2 system has a new function that automatically selects representative images from a full MRI stack. RESULTS: The average segmentation performance of the fivefold cross-validation was measured via the intersection of union method, resulting in performance values of 0.743 (SD 0.030) for the 3into3Inception network and 0.811 (SD 0.032) for the 3intoUNet network. The representative magnetic resonance slices (ie, from a data set of unseen magnetic resonance images) that were automatically selected by the INHEARIT-v2 system only differed from a maximum of 2 expert-selected slices. After comparing the ratios calculated by experienced physicians and those calculated by the INHEARIT-v2 system, we found that the average intraclass correlation coefficient for all cases was 0.941; the average intraclass correlation coefficient of the vestibules was 0.968, and that of the cochleae was 0.914. The time required for the fully automated system to accurately analyze EH ratios based on a patient's MRI stack was approximately 3.5 seconds. CONCLUSIONS: In this study, a fully automated full-stack magnetic resonance analysis system for measuring EH ratios was developed (named INHEARIT-v2), and the results showed that there was a high correlation between the expert-calculated EH ratio values and those calculated by the INHEARIT-v2 system. The system is an upgraded version of the INHEARIT system; it has higher segmentation performance and automatically selects representative images from an MRI stack. The new model can help clinicians by providing objective analysis results and reducing the workload for interpreting magnetic resonance images.

Prediction of Drill Bit Breakage Using an Infrared Sensor.

In this paper, a novel drill bit breakage prediction method featuring a low-cost commercial infrared sensor to monitor drill bit corner wear is proposed. In the proposed method, the drill bit outer corner wear state can be monitored by measuring reflected infrared light because the reflection phenomenon is influenced by wear, edge shape, and surface roughness of the drill bit. In the experiments, a titanium workpiece was drilled without using cutting fluid to accelerate drill bit fracture. After drilling a hole in the workpiece, reflected infrared light was measured for the drill bit rotating at 100 rpm. Collected data on intensity of infrared light reflected from the circumferential surface of the drill bit versus the rotation angle of the drill bit were considered to predict tool breakage; two significant positions to predict tool breakage were found from the reflected infrared light graphs. By defining gradient vectors from the slopes of the reflected infrared light curves, a reliable criterion for determining drill bit breakage could be established. The proposed method offers possibilities for new measurement and analysis methods that have not been used in conventional tool wear and damage studies. The advantage of the proposed method is that the measurement device is easy to install and the measured signal is resistant to electromagnetic noise and ambient temperature because optical fiber is used as the signal transmission medium. It also eliminates the need for complex analysis of the measured signal, eliminating the need for a high-performance analyzer and reducing analysis time.

Modulation of Cellular NAD+ Attenuates Cancer-Associated Hypercoagulability and Thrombosis via the Inhibition of Tissue Factor and Formation of Neutrophil Extracellular Traps.

Cancer-associated thrombosis is the second-leading cause of mortality in patients with cancer and presents a poor prognosis, with a lack of effective treatment strategies. NAD(P)H quinone oxidoreductase 1 (NQO1) increases the cellular nicotinamide adenine dinucleotide (NAD+) levels by accelerating the oxidation of NADH to NAD+, thus playing important roles in cellular homeostasis, energy metabolism, and inflammatory responses. Using a murine orthotopic 4T1 breast cancer model, in which multiple thrombi are generated in the lungs at the late stage of cancer development, we investigated the effects of regulating the cellular NAD+ levels on cancer-associated thrombosis. In this study, we show that dunnione (a strong substrate of NQO1) attenuates the prothrombotic state and lung thrombosis in tumor-bearing mice by inhibiting the expression of tissue factor and formation of neutrophil extracellular traps (NETs). Dunnione increases the cellular NAD+ levels in lung tissues of tumor-bearing mice to restore the declining sirtuin 1 (SIRT1) activity, thus deacetylating nuclear factor-kappa B (NF-κB) and preventing the overexpression of tissue factor in bronchial epithelial and vascular endothelial cells. In addition, we demonstrated that dunnione abolishes the ability of neutrophils to generate NETs by suppressing histone acetylation and NADPH oxidase (NOX) activity. Overall, our results reveal that the regulation of cellular NAD+ levels by pharmacological agents may inhibit pulmonary embolism in tumor-bearing mice, which may potentially be used as a viable therapeutic approach for the treatment of cancer-associated thrombosis.

Nanopatterned Nafion microelectrode arrays for in vitro cardiac electrophysiology.

In this study, we report nanopatterned Nafion microelectrode arrays for in vitro cardiac electrophysiology. With the aim of defining sophisticated Nafion nanostructures with highly ionic conductivity, fabrication parameters such as Nafion concentration and curing temperature were optimized. By increasing curing temperature and Nafion concentration, we were able to control the replication fidelity of Nafion nanopatterns when copied from a PDMS master mold. We also found that cross-sectional morphology and ion current density of nanopatterned Nafion strongly depends on the fabrication parameters. To investigate this dependency, current-voltage analysis was conducted using organic electrochemical transistors (OECT) overlaid with patterned Nafion substrates. Nanopatterned Nafion was found to allow higher ion current densities than unpatterned surfaces. Furthermore, higher curing temperatures were found to render Nafion layers with higher ion/electrical transfer properties. To optimize nanopattern dimensions, electrical current flows, and film uniformity, a final configuration consisting of 5% nanopatterned Nafion cured at 65°C was chosen. Multielectrode arrays (MEAs) were then covered with optimized Nafion nanopatterns and used for electrophysiological analysis of two types of induced pluripotent stem cell-derived cardiomyocytes (iPSCs-CMs). These data highlight the suitability of nanopatterned Nafion, combined with MEAs, for enhancing the cellular environment of iPSC-CMs for use in electrophysiological analysis in vitro.

Diagnostic accuracy of MR imaging of patients with leptomeningeal seeding from lung adenocarcinoma based on 2017 RANO proposal: added value of contrast-enhanced 2D axial T2 FLAIR.

PURPOSE: We purposed to compare diagnostic accuracy of contrast-enhanced (CE) 3D T1-weighted fast field echo (3D T1-WI), CE 2D spin echo T1-weighted image (2D T1-WI), and CE 2D T2 FLAIR on evaluation of leptomeningeal metastasis(LM) using detailed features suggested in RANO proposal in a homogeneous group with cytology-proven LM. METHODS: Thirty-five lung adenocarcinoma patients with CSF cytology-proven leptomeningeal metastasis were enrolled in this retrospective analysis, who were enrolled in the prospective study (NCT03257124). MR images including CE 3D T1-WI, CE 2D T1-WI, and CE 2D FLAIR were reviewed. Presence of leptomeningeal nodule, leptomeningeal enhancement, and cranial nerve enhancement was evaluated according to the RANO proposal. Diagnostic accuracy of each sequence was compared and added value of CE 2D FLAIR to CE 3D T1-WI was evaluated. RESULTS: Two patients had unmeasurable small nodules recognized on 3D T1-WI only. Leptomeningeal enhancement was positive in 60%, 60%, and 77.1%, cranial nerve enhancement was positive in 51.4%, 45.7%, and 68.6% of the patients on 3D T1-WI, 2D T1-WI, and 2D FLAIR, respectively. Overall sensitivity for detection of LM was 71.4%, 71.4%, and 82.9% on 3D T1-WI, 2D T1-WI, and 2D FLAIR. When adding 2D FLAIR to 3D T1-WI, overall sensitivity for detection of LM was 82.9%. CONCLUSION: 3D T1-WI is the best for identifying leptomeningeal nodules. The sensitivity of 2D FLAIR is the highest for both LNE and CNE. Since both sequences are complementary, it can be helpful to take both sequences. Checking each feature according to the RANO proposal, especially CNE, may help you not to miss LM.

Tropical forcing of the recent rapid Arctic warming in northeastern Canada and Greenland.

Rapid Arctic warming and sea-ice reduction in the Arctic Ocean are widely attributed to anthropogenic climate change. The Arctic warming exceeds the global average warming because of feedbacks that include sea-ice reduction and other dynamical and radiative feedbacks. We find that the most prominent annual mean surface and tropospheric warming in the Arctic since 1979 has occurred in northeastern Canada and Greenland. In this region, much of the year-to-year temperature variability is associated with the leading mode of large-scale circulation variability in the North Atlantic, namely, the North Atlantic Oscillation. Here we show that the recent warming in this region is strongly associated with a negative trend in the North Atlantic Oscillation, which is a response to anomalous Rossby wave-train activity originating in the tropical Pacific. Atmospheric model experiments forced by prescribed tropical sea surface temperatures simulate the observed circulation changes and associated tropospheric and surface warming over northeastern Canada and Greenland. Experiments from the Coupled Model Intercomparison Project Phase 5 (ref. 16) models with prescribed anthropogenic forcing show no similar circulation changes related to the North Atlantic Oscillation or associated tropospheric warming. This suggests that a substantial portion of recent warming in the northeastern Canada and Greenland sector of the Arctic arises from unforced natural variability.

Augmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiac dysfunction in mice.

BACKGROUND: Adriamycin (ADR) is a powerful chemotherapeutic agent extensively used to treat various human neoplasms. However, its clinical utility is hampered due to severe adverse side effects i.e. cardiotoxicity and heart failure. ADR-induced cardiomyopathy (AIC) has been reported to be caused by myocardial damage and dysfunction through oxidative stress, DNA damage, and inflammatory responses. Nonetheless, the remedies for AIC are even not established. Therefore, we illustrate the role of NAD+/NADH modulation by NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action on AIC. METHODS AND RESULTS: AIC was established by intraperitoneal injection of ADR in C57BL/6 wild-type (WT) and NQO1 knockout (NQO1-/-) mice. All Mice were orally administered dunnione (named NQO1 substrate) before and after exposure to ADR. Cardiac biomarker levels in the plasma, cardiac dysfunction, oxidative biomarkers, and mRNA and protein levels of pro-inflammatory mediators were determined compared the cardiac toxicity of each experimental group. All biomarkers of Cardiac damage and oxidative stress, and mRNA levels of pro-inflammatory cytokines including cardiac dysfunction were increased in ADR-treated both WT and NQO1-/- mice. However, this increase was significantly reduced by dunnione in WT, but not in NQO1-/- mice. In addition, a decrease in SIRT1 activity due to a reduction in the NAD+/NADH ratio by PARP-1 hyperactivation was associated with AIC through increased nuclear factor (NF)-κB p65 and p53 acetylation in both WT and NQO1-/- mice. While an elevation in NAD+/NADH ratio via NQO1 enzymatic action using dunnione recovered SIRT1 activity and subsequently deacetylated NF-κB p65 and p53, however not in NQO1-/- mice, thereby attenuating AIC. CONCLUSION: Thus, modulation of NAD+/NADH by NQO1 may be a novel therapeutic approach to prevent chemotherapy-associated heart failure, including AIC.

Airway epithelial phosphoinositide 3-kinase-δ contributes to the modulation of fungi-induced innate immune response.

BACKGROUND: Respiratory fungal exposure is known to be associated with severe allergic lung inflammation. Airway epithelium is an essential controller of allergic inflammation. An innate immune recognition receptor, nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome, and phosphoinositide 3 kinase (PI3K)-δ in airway epithelium are involved in various inflammatory processes. OBJECTIVES: We investigated the role of NLRP3 inflammasome in fungi-induced allergic lung inflammation and examined the regulatory mechanism of NLRP3 inflammasome, focusing on PI3K-δ in airway epithelium. METHODS: We used two in vivo models induced by exposure to Aspergillus fumigatus (Af) and Alternaria alternata (Aa), as well as an Af-exposed in vitro system. We also checked NLRP3 expression in lung tissues from patients with allergic bronchopulmonary aspergillosis (ABPA). RESULTS: Assembly/activation of NLRP3 inflammasome was increased in the lung of Af-exposed mice. Elevation of NLRP3 inflammasome assembly/activation was observed in Af-stimulated murine and human epithelial cells. Similarly, pulmonary expression of NLRP3 in patients with ABPA was increased. Importantly, neutralisation of NLRP3 inflammasome derived IL-1ß alleviated pathophysiological features of Af-induced allergic inflammation. Furthermore, PI3K-δ blockade improved Af-induced allergic inflammation through modulation of NLRP3 inflammasome, especially in epithelial cells. This modulatory role of PI3K-δ was mediated through the regulation of mitochondrial reactive oxygen species (mtROS) generation. NLRP3 inflammasome was also implicated in Aa-induced eosinophilic allergic inflammation, which was improved by PI3K-δ blockade. CONCLUSION: These findings demonstrate that fungi-induced assembly/activation of NLRP3 inflammasome in airway epithelium may be modulated by PI3K-δ, which is mediated partly through the regulation of mtROS generation. Inhibition of PI3K-δ may have potential for treating fungi-induced severe allergic lung inflammation.

Multicenter, randomized single-port versus multiport laparoscopic surgery (SIMPLE) trial in colon cancer: an interim analysis.

BACKGROUND: Single-port laparoscopic surgery (SPLS) was recently introduced as an innovative minimally invasive surgery method. Retrospective studies have revealed the safety and feasibility of SPLS for colon cancer treatment. However, no prospective randomized trials have been performed. The multicenter, randomized SIMPLE (single-port versus multiport laparoscopic surgery) trial aimed to investigate short-term perioperative outcomes of SPLS for colon cancer treatment, compared with multiport laparoscopic surgery (MPLS). METHODS: Between August 2011 and April 2014, a total of 194 patients with colon cancer were recruited from seven hospitals in Korea. Patients were randomly allocated into the SPLS group (n = 99) or MPLS group (n = 95). The primary endpoint was postoperative complications. Operative, postoperative, and pathologic outcomes were analyzed after 50% of the patient study population had been recruited. RESULTS: The patients' demographic characteristics, operative times, estimated blood volume losses, numbers of harvested lymph nodes, and lengths of both resection margins were not significantly different between groups. In the SPLS group, the rates of conversion to MPLS and open surgery were 12.9 and 2.2%, respectively. Postoperative complications occurred in 10.8% of the SPLS, and 12.5% of the MPLS patients (p = 0.714). Times to functional recovery, pain scores, and amounts of analgesia were similar between groups. CONCLUSION: The results of this interim analysis suggested that SPLS is technically safe and appropriate when used for radical resection of colon cancer. (ClinicalTrials.gov Identifier: NCT01480128).

Structural and Electrical Characteristics of Carbon Nanowalls Synthesized on the Polyimide Film.

In this study, the structural and electrical characteristics of carbon nanowalls (CNWs) synthesized on polyimide films were investigated. CNWs were synthesized on polyimide films as various growth times. The cross-section and surface of the CNWs synthesized were examined using FE-SEM. The growth and defects of CNWs were observed by raman spectrum. The hall measurement system was used to analyzed sheet resistance, resistivity and conductivity. The CNWs synthesized at 40 minutes showed outstanding structural and electrical characterizations than another growth times.

Development and Performance Analysis of Carbon Nanowall-Based Mass Sensor.

In this study, a mass sensor was fabricated using a carbon nanowalls, and its performance was analyzed. The substrate that was used to fabricate the mass sensor was a polyimide film, on which a SiO2 insulating layer and a copper electrode were deposited using an RF magnetron sputter. Thereafter, a carbon nanowalls was grown on the substrate until its size was 5 by 5 mm. The growth times of the completely grown carbon nanowalls were 20, 25, and 30 minutes, respectively. The performance of the mass sensors fabricated based on different carbon nanowalls grown for various growth times was analyzed according to the changing mass from 1 to 5 mg.

Detection of Actin Filament and Cofilin Interaction Change by Actin Filament Curvature Decreasing.

Actin filament senses mechanical forces and it is transduced into biochemical signals during many cellular processes. In the disassembling process of actin filaments, cofilin plays a central role as the actin filament depolymerization. In this study, we evaluated a quantitative analysis of the actin filament-cofilin interaction change dependent upon the actin filament curvature decrease using atomic force microscopy (AFM) and a fabricated wave-like substrate. A wave-like substrate was fabricated by a maskless photo-lithography of a spin coated film on a glass substrate, and graphene oxide sheet was used for the decreasing of non-specific interaction between protein and the substrate. By single-molecule force spectroscopy, we determined rupture force of actin filament-cofilin binding on the wave-like substrate and a flat substrate. The rupture force of actin filament-cofilin binding at the curvature of -1.35 µm-1 showed a value approximately 4 times higher than the rupture force at the curvature of -0.15 µm-1. The present study will provide the possibility and quantitative evidence that mechanical stress on cytoskeletal filaments can modulate how they interact with their binding proteins.