Ultrastrong and ductile steel welds achieved by fine interlocking microstructures with film-like retained austenite.

The degradation of mechanical properties caused by grain coarsening or the formation of brittle phases during welding reduces the longevity of products. Here, we report advances in the weld quality of ultra-high strength steels by utilizing Nb and Cr instead of Ni. Sole addition of Cr, as an alternative to Ni, has limitations in developing fine weld microstructure, while it is revealed that the coupling effects of Nb and Cr additions make a finer interlocking weld microstructures with a higher fraction of retained austenite due to the decrease in austenite to acicular ferrite and bainite transformation temperature and carbon activity. As a result, an alloying design with Nb and Cr creates ultrastrong and ductile steel welds with enhanced tensile properties, impact toughness, and fatigue strength, at 45% lower material costs and lower environmental impact by removing Ni.

The traditional herbal medicines mixture, Banhasasim-tang, relieves the symptoms of irritable bowel syndrome via modulation of TRPA1, NaV1.5 and NaV1.7 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: The cause of irritable bowel syndrome (IBS), a functional gastrointestinal (GI) disorder, remains unclear. Banhasasim-tang (BHSST), a traditional herbal medicines mixture, mainly used to treat GI-related diseases, may have a potential in IBS treatment. IBS is characterized by abdominal pain as the main clinical symptom, which seriously affects the quality of life. AIM OF THE STUDY: We conducted a study to evaluate the effectiveness of BHSST and its mechanisms of action in treating IBS. MATERIALS AND METHODS: We evaluated the efficacy of BHSST in a zymosan-induced diarrhea-predominant animal model of IBS. Electrophysiological methods were used to confirm modulation of transient receptor potential (TRP) and voltage-gated Na+ (NaV) ion channels, which are associated mechanisms of action. RESULTS: Oral administration of BHSST decreased colon length, increased stool scores, and increased colon weight. Weight loss was also minimized without affecting food intake. In mice administered with BHSST, the mucosal thickness was suppressed, making it similar to that of normal mice, and the degree of tumor necrosis factor-α was severely reduced. These effects were similar to those of the anti-inflammatory drug-sulfasalazine-and antidepressant-amitriptyline. Moreover, pain-related behaviors were substantially reduced. Additionally, BHSST inhibited TRPA1, NaV1.5, and NaV1.7 ion channels associated with IBS-mediated visceral hypersensitivity. CONCLUSIONS: In summary, the findings suggest that BHSST has potential beneficial effects on IBS and diarrhea through the modulation of ion channels.

[6]-Gingerol induces Caspase-Dependent Apoptosis in Bladder Cancer cells via MAPK and ROS Signaling.

The anti-cancer effects of [6]-gingerol ([6]-GIN), the main active polyphenol of ginger (Zingiber officinale), were investigated in the human bladder cancer cell line 5637. [6]-GIN inhibited cell proliferation, increased sub­G1 phase ratios, and depolarized mitochondrial membrane potential. [6]-GIN-induced cell death was associated with the downregulation of B­cell lymphoma 2 (BCL­2) and survivin and the upregulation of Bcl­2­associated X protein (Bax). [6]-GIN activated caspase­3 and caspase-9 and regulated the activation of mitogen-activated protein kinases (MAPKs). Further, [6]-GIN also increased the intracellular reactive oxygen species (ROS) levels and TG100-115 or tranilast increased [6]-GIN­induced cell death. These results suggest that [6]-GIN induced apoptosis in the bladder cancer cell line 5637 and therefore has the potential to be used in the development of new drugs for bladder cancer treatment.

Surface ECG-based complexity parameters for predicting outcomes of catheter ablation for nonparoxysmal atrial fibrillation: efficacy of fibrillatory wave amplitude.

Catheter ablation (CA) is a well-established therapy for rhythm control in atrial fibrillation (AF). However, CA outcomes for persistent AF remain unsatisfactory because of the high recurrence rate despite time-consuming efforts and the latest ablation technology. Therefore, the selection of good responders to CA is necessary. Surface electrocardiography (sECG)-based complexity parameters were tested for the predictive ability of procedural termination failure during CA and late recurrence of atrial arrhythmias (AA) after CA. A total of 130 patients with nonparoxysmal AF who underwent CA for the first time were investigated. A 10-second sECG of 4 leads (leads I, II, V1, and V6) was analyzed to compute the fibrillatory wave amplitude (FWA), dominant frequency (DF), spectral entropy (SE), organization index (OI), and sample entropy (SampEn). The study endpoints were procedural termination failure during CA and late (≥1 year) AA recurrence after CA. In the multivariate analysis, FWA in lead V1 and DF in lead I were independent predictors of successful AF termination during CA (P <.05). The optimal cut-off values for FWA in lead V1 and DF in lead I were 60.38 µV (area under the curve [AUC], 0.672; P = .001) and 5.7 Hz (AUC, 0.630; P = .016), respectively. The combination of FWA of lead V1 and DF of lead I had a more powerful odds ratio for predicting procedural termination failure (OR, 8.542; 95% CI, 2.938-28.834; P < .001). FWA in lead V1 was the only independent predictor of late recurrence after CA. The cut-off value is 65.73 µV which was 0.634 of the AUC (P = .009). These sECG parameters, FWA in lead V1 and DF in lead I, predicted AF termination by CA in patients with nonparoxysmal AF. In particular, FWA in lead V1 was an independent predictor of late recurrence of AA after CA.

Grape seed powder increases gastrointestinal motility.

Grape seed is an important natural bioactive product with various health benefits. Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI) tract. The present study investigated the effects of grape seed powder (GSP) on ICC properties and GI motility. GSP depolarized the pacemaker potentials of ICCs in a dose­dependent manner. Y25130 or SB269970 slightly inhibited GSP­induced effects. However, Y25130 and SB269970 together completely blocked GSP-induced effects. In the presence of inhibitors of protein kinase C, protein kinase A, or mitogen-activated protein kinase, GSP­induced ICC depolarization was inhibited. GSP increased the intestinal transit rate in normal mice and in mice with acetic acid-induced GI motility disorder. In addition, the levels of motilin and substance P were elevated after GSP dosing. These results demonstrate that GSP can regulate GI motility, and therefore, it is a potential therapeutic agent for treating GI motility disorders.

Effects of black garlic on the pacemaker potentials of interstitial cells of Cajal in murine small intestine in vitro and on gastrointestinal motility in vivo.

Black garlic (BG) is a newly explored food stuff obtained via fermentation of raw, healthy garlic, especially in Asian countries. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal (GI) motility. The purpose of this study was to investigate the effects of BG extract on the pacemaker potentials of the ICC in the small intestines of mice and the possibility of controlling GI motility. The antioxidant activity of BG extract was also investigated. The whole-cell electrophysiological method was used to measure pacemaker potentials of the ICC in vitro, whereas GI motility was measured using the intestinal transit rate (ITR) in vivo. BG extract depolarized the pacemaker potentials of the ICC. Y25130 and RS39604 5-HT receptor antagonists could not inhibit the effect of BG extract on the pacemaker potentials of the ICC, whereas the 5-HT receptor antagonist SB269970 could. Pre-treatment with external Na+ (5 mM) or Ca2+-free solution inhibited the BG extract-induced depolarization of the ICC. With SB203580, PD98059, or c-jun NH2-terminal kinase II inhibitor pre-treatment, BG extract did not induce pacemaker potential depolarization. Moreover, the ITR values were increased by BG extract. Elevation of the ITR due to BG extract was related with increased protein expression of the 5-HT7 receptors. In addition, BG extract showed antioxidant activity. Collectively, these results highlight the ability of BG extract to regulate GI motility and the possibility of using it to develop GI motility modulators in the future. Moreover, BG showed immense potential as an antioxidant.

Alisma canaliculatum Extract Affects AGS Gastric Cancer Cells by Inducing Apoptosis.

The anti-cancer effects of Alisma canaliculatum extracts (ACE) were identified in AGS gastric cancer cells. Our results showed that ACE inhibited the growth of AGS cells, increased the proportion of sub-G1 phase cells, and depolarized the membrane potential of mitochondria. ACE-induced gastric cancer cell death was associated with Bcl-2, survivin and Bax level changes, and it activated caspase-3 and -9. In addition, it was involved in the activation of MAPKs and increased the reactive oxygen species (ROS). These results suggest that ACE induces apoptosis in AGS gastric cancer cells, and therefore, ACE may have the potential to treat gastric cancer.

Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca2+ and Na+ influx.

Interstitial cells of Cajal (ICCs) are pacemaker cells that control smooth muscle contraction in the gastrointestinal (GI) tract. The present study investigated the effects of Salvia miltiorrhiza (SM) on the pacemaker potentials of ICCs from the mouse small intestine in vitro and on GI motility in vivo. The whole­cell patch­clamp configuration was used to record pacemaker potential in ICCs in vitro, and GI motility was investigated in vivo by recording intestinal transit rate (ITR). Using the whole­cell patch­clamp configuration, SM depolarized the pacemaker potentials of ICCs in a dose­dependent manner. Fulvestrant blocked SM­induced effects but 1,3­dihydro­3,3­bis(4­hydroxyphenyl)-7-methyl­2H­indol­2­one did not. Additionally, 4­[2­phenyl-5,7­bis(trifluoromethyl) pyrazolo[1,5­a]pyrimidin­3­yl] phenol blocked SM­induced effects. Intracellular guanosine 5'­O­(2­thiodiphosphate), and pretreatment with extracellular Ca2+­ and Na+­free solutions also blocked SM­induced effects. Furthermore, ITR values were increased by SM in vivo and SM elevated the levels of motilin (MTL). The SM­induced increase in ITR was associated with increased protein expression levels of c­kit and the transmembrane protein 16A (TMEM16A) channel. In addition, SM induced pacemaker potential depolarization through estrogen receptor ß in a G protein­dependent manner via extracellular Ca2+ and Na+ regulation in the murine small intestine in vitro. Moreover, SM increased the ITR in vivo through the MTL hormone via c­kit and TMEM16A­dependent pathways. Taken together, these results suggested that SM may have the ability to control GI motility and could be used as a GI motility regulator.

Apoptotic effects of alisol B 23­acetate on gastric cancer cells.

Alisol B 23­acetate (AB23A) is a natural triterpenoid isolated from Alismatis rhizoma, which exhibits a number of pharmacological activities. In the present study, AB23A­induced anticancer efficacy was examined in AGS gastric cancer cells. Cell viability assay, cell cycle analysis, caspase activity assay, western blotting and reactive oxygen species (ROS) assay were used to investigate the anticancer effects of AB23A on AGS cells. AB23A reduced the viability of AGS cells, increased the sub­G1 cell fraction and depolarized the mitochondrial membrane. Notably, AB23A­induced cell death was associated with downregulation of the B­cell lymphoma 2 and survivin proteins, and upregulation of the Bax protein. In addition, AB23A increased caspase­3 and ­9 activities, and regulated the activation of mitogen­activated protein kinases (MAPK). Moreover, AB23A increased the production of reactive oxygen species. These results suggested that AB23A may induce apoptosis through cell cycle arrest and the mitochondrial pathway, accompanied by the caspase and MAPK signaling cascades. In conclusion, AB23A may have potential as a novel anticancer drug for the treatment of gastric cancer.

Radix Sophorae Flavescentis induces apoptosis through by Caspase, MAPK Activation and ROS Signaling Pathways in 5637 Human Bladder Cancer Cells.

The anti-cancer mechanisms of Radix Sophorae Flavescentis were investigated in 5637 bladder cancer cells. Radix Sophorae Flavescentis extract (RSF) (50­400 µg/ml) inhibited the proliferation of 5637 cells and increased sub­G1 phase ratios. RSF­induced cell death was associated with the down-regulation of B­cell lymphoma 2 (Bcl­2) and the up-regulation of Bcl­2 X­associated protein (Bax). RSF also activated caspase­3 and -9 and regulated the activations of mitogen-activated protein kinases (MAPKs). In addition, RSF increased intracellular reactive oxygen species (ROS) levels and depolarized the mitochondrial membrane potential. These findings suggest RSF induces apoptosis in 5637 bladder cancer cells and that it has potential use as a novel anti-cancer drug for bladder cancer.

Radix Sophorae Flavescentis inhibits proliferation and induces apoptosis of AGS human gastric cancer cells.

Traditional herbal medicines are being increasingly used worldwide to treat cancer. Radix Sophorae Flavescentis (RSF) is a Chinese herb, which has numerous pharmacological properties, including anti­tumour effects. In this study, we investigated the mechanisms underlying RSF­induced apoptosis in human gastric cancer cells (AGS cells). We found that RSF treatment (20­200 µg/ml) inhibited the proliferation of AGS cells and increased the sub­G1 phase ratio. RSF­induced cell death was associated with the downregulation of BCl­2 and upregulation of Bax. In addition to increasing the expression levels of apoptosis­mediating surface antigen FAS and Fas ligand, RSF also activated caspase­3; however, mitogen­activated protein kinase appeared to inhibit RSF­induced cell death. RSF also led to an increased production of reactive oxygen species. Based on these results, we propose that RSF could be a potential therapeutic agent for gastric cancer.

Dapsone modulates lipopolysaccharide-activated bone marrow cells by inducing cell death and down-regulating tumor necrosis factor-α production.

Dapsone, an antibiotic, has been used to cure leprosy. It has been reported that dapsone has anti-inflammatory activity in hosts; however, the anti-inflammatory mechanism of dapsone has not been fully elucidated. The present study investigated the anti-inflammatory effects of dapsone on bone marrow cells (BMs), especially upon exposure to lipopolysaccharide (LPS). We treated BMs with LPS and dapsone, and the treated cells underwent cellular activity assay, flow cytometry analysis, cytokine production assessment, and reactive oxygen species assay. LPS distinctly activated BMs with several characteristics including high cellular activity, granulocyte changes, and tumor necrosis factor alpha (TNF-α) production increases. Interestingly, dapsone modulated the inflammatory cells, including granulocytes in LPS-treated BMs, by inducing cell death. While the percentage of Gr-1 positive cells was 57% in control cells, LPS increased that to 75%, and LPS plus dapsone decreased it to 64%. Furthermore, dapsone decreased the mitochondrial membrane potential of LPS-treated BMs. At a low concentration (25 µg/mL), dapsone significantly decreased the production of TNF-α in LPS-treated BMs by 54%. This study confirmed that dapsone has anti-inflammatory effects on LPS-mediated inflammation via modulation of the number and function of inflammatory cells, providing new and useful information for clinicians and researchers.

Optimizing Prone Cardiopulmonary Resuscitation: Identifying the Vertebral Level Correlating With the Largest Left Ventricle Cross-Sectional Area via Computed Tomography Scan.

BACKGROUND: Placing the patient in the prone position frequently is required for some surgical procedures. If cardiac arrest occurs and the patient cannot be safely turned supine, cardiopulmonary resuscitation (CPR) may need to be performed with the patient in the prone position. Although clear landmarks have been defined for supine CPR, the optimal hand position for CPR in the prone position has not been clearly determined. The purpose of this study was to determine anatomically the optimal hand position for CPR in the prone position. METHODS: We reviewed retrospectively the chest computed tomography images of 100 patients taken in the prone position. The vertebral body levels crossing the medial angle of the scapula, the inferior angle of the scapula, and the spinous process of the vertebral body connected to the most inferior rib were identified, and we selected the image level at which the left ventricular (LV) cross-sectional area was the largest. This level was defined as the optimal compression level and correlated to surface anatomical landmarks. We calculated the ratio of the distance from the C7 spinous process to the level of the largest LV cross-sectional area divided by the distance from the C7 spinous process to the spinous process of the vertebral body connected with the most inferior rib. RESULTS: The level of the largest LV cross-sectional area in the prone position was 1 vertebral segment below the inferior angle of the scapula in 45% (99% confidence interval [CI], 33-58) of patients and 0 to 2 vertebral segments below that in 95% (99% CI, 86-98) of patients. The mean (SD) ratio of the distance from the C7 spinous process to the level of the largest LV cross-sectional area divided by the distance from the C7 spinous process to T12 spinous process was 67% ± 7% (99% CI, 65-69). CONCLUSIONS: When the patient is positioned prone, the largest LV cross-sectional area is 0 to 2 vertebral segments below the inferior angle of the scapula in at least 86% of patients. Further studies are needed to determine whether this position is optimal for chest compressions in the prone position.

Tanshinone I induces cyclin D1 proteasomal degradation in an ERK1/2 dependent way in human colorectal cancer cells.

Tanshinone I (TAN I) as one of the naturally occurring diterpenes from Salvia miltiorrhizae Bunge (Danshen) has been reported to exhibit an anti-cancer activity. However, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to elucidate the biological mechanism by which TAN I may induce the inhibition of cell growth in human colorectal cancer cells. The treatment of TAN I suppressed the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. However, the mRNA level of cyclin D1 did not changed by TAN I treatment. Inhibition of proteasomal degradation by MG132 blocked TAN I-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with TAN I. In addition, phosphorylation of cyclin D1 at threonine-286 was increased by TAN I and a point mutation of threonine-286 to alanine attenuated TAN I-mediated cyclin D1 downregulation. Inhibition of ERK1/2 suppressed cyclin D1 phosphorylation and subsequent downregulation by TAN I. From these results, we suggest that TAN I-mediated cyclin D1 downregulation may result from proteasomal degradation through its ERK1/2-mediated phosphorylation of threonine-286. In conclusion, the current study provides new mechanistic link between TAN I, cyclin D1 downregulation and cell growth in human colorectal cancer cells.

Optimization of principal-component-analysis-applied in situ spectroscopy data using neural networks and genetic algorithms.

A new model of multidimensional in situ diagnostic data is presented. This was accomplished by combining a back-propagation neural network (BPNN), principal component analysis (PCA), and a genetic algorithm (GA). The PCA was used to reduce input dimensionality. The GA was applied to search for a set of optimized training factors involved in BPNN training. The presented technique was evaluated with optical emission spectroscopy (OES) data measured during the etching of oxide thin films in a CHF(3)-CF(4) inductively coupled plasma. For a systematic modeling, the etching process was characterized by a face-centered Box Wilson experiment. The etch responses to be modeled include oxide etch rate, oxide profile angle, and oxide etch rate non-uniformity. In PCA, three types of data variances were employed and the reduced input dimensionality corresponding to 100, 99, and 98% are 16, 8, and 5. The BPNN training factors to be optimized include the training tolerance, number of hidden neurons, magnitude of initial weight distribution, gradient of bipolar sigmoid function, and gradient of linear function. The prediction errors of GA-BPNN models are 249 A/min, 2.64 degrees, and 0.439% for the etch rate, profile angle, and etch rate non-uniformity, respectively. Compared to the conventional and previous full OES models, the presented models demonstrated a significantly improved prediction for all etch responses.