Search

Foodborne pathogenic gram-negative bacteria are major causes of diseases in human populations worldwide. Removing these infectious bacteria are mainly done using appropriate sterilization technologies. One target for sterilization is the outer membrane of gram-negative bacteria which are crucial for growth and survival. The outer membrane of gram-negative bacteria is composed of outer membrane protein (OMPs), Lipproteins (Lpp) and Lipopolysaccharides (LPS), which depend on specific transmembrane transport systems, such as β-Barrel Assembly Machinery (Bam), Localization of Lipoprotein (Lol) and lipopolysaccharide transport system (Lpt). In this outlook paper, we review, initially, standard sterilization technologies in the field of food safety. Then the novel sterilizing agents targeting outer membrane biogenesis in gram-negative bacteria will be summarized and highlighted. We hope this review can provide new insights for developing novel food sterilization technologies.

Homologous recombination (HR) repair is an important determinant of chemosensitivity. However, the mechanisms underlying HR regulation remain largely unknown. Cysteine-rich intestinal protein 1 (CRIP1) is a member of the LIM/double-zinc finger protein family and is overexpressed and associated with prognosis in several tumor types. However, to date, the functional role of CRIP1 in cancer biology is poorly understood. Here we found that CRIP1 downregulation causes HR repair deficiency with concomitant increase in cell sensitivity to cisplatin, epirubicin, and the poly ADP-ribose polymerase (PARP) inhibitor olaparib in gastric cancer cells. Mechanistically, upon DNA damage, CRIP1 is deubiquitinated and upregulated by activated AKT signaling. CRIP1, in turn, promotes nuclear enrichment of RAD51, which is a prerequisite step for HR commencement, by stabilizing BRCA2 to counteract FBXO5-targeted RAD51 degradation and by binding to the core domain of RAD51 (RAD51184–257) in coordination with BRCA2, to facilitate nuclear export signal masking interactions between BRCA2 and RAD51. Moreover, through mass spectrometry screening, we found that KPNA4 is at least one of the carriers controlling the nucleo-cytoplasmic distribution of the CRIP1–BRCA2–RAD51 complex in response to chemotherapy. Consistent with these findings, RAD51 inhibitors block the CRIP1-mediated HR process, thereby restoring chemotherapy sensitivity of gastric cancer cells with high CRIP1 expression. Analysis of patient specimens revealed an abnormally high level of CRIP1 expression in GC tissues compared to that in the adjacent normal mucosa and a significant negative association between CRIP1 expression and survival time in patient cohorts with different types of solid tumors undergoing genotoxic treatments. In conclusion, our study suggests an essential function of CRIP1 in promoting HR repair and facilitating gastric cancer cell adaptation to genotoxic therapy.

Background Depression is a common, easily ignored, accompanied disease of gastric cancer (GC) patients and is often observed with elevated plasma catecholamine levels. Depression frequently promotes GC progression and leads to poor clinical outcomes; however, the molecular mechanisms underlying depression‐induced GC progression remain poorly understood. We aimed to study the effects of depression on GC progression and explore possible mechanisms mediating the action of depression‐associated catecholamines on GC. Methods Depression states of GC patients were graded using the Patient Health Questionnaire‐9, and plasma catecholamine levels were examined by high performance liquid chromatography coupled with tandem mass spectrometry. Migrative and invasive GC cells were examined using transwell assays, and metastatic GC niches were imaged using bioluminescence technology in a depression mouse model established with chronic unpredictable mild stress. Mouse depression‐like behaviors were assessed through sucrose preference, forced swimming, and tail suspension tests. Characteristics of the neuroendocrine phenotype were observed via RT‐PCR, Western blotting, flow cytometry, and transmission electron microscopy. Results Fifty‐one GC patients (age: 53.61 ± 1.79 years; cancer duration: 3.71 ± 0.33 months; depression duration: 2.37 ± 0.38 months; male‐to‐female ratio: 1.55:1) were enrolled in the study. Depression grade was significantly higher in GC patients showing higher plasma levels of catecholamines (epinephrine: P = 0.018; noradrenaline: P = 0.009), higher oncogene metastasis‐associated in colon cancer‐1 (MACC1) level (P = 0.018), and metastasis (P < 0.001). Further, depression‐associated catecholamine specifically bound to the beta‐2 adrenergic receptor (β2‐AR) and upregulated MACC1 expression, and thus promoting neuroendocrine phenotypic transformation through direct binding between MACC1 and synaptophysin. Eventually, the neuroendocrine phenotypic transformation accelerated GC invasion in vitro and metastasis in vivo. However, β2‐AR antagonist ICI‐118,551 or MACC1 silencing effectively blocked the catecholamine‐induced neuroendocrine phenotypic transformation and eliminated depression‐enhanced GC migration and invasion. Moreover, β2‐AR blocking or MACC1 silencing prevented GC metastasis attributed to a neuroendocrine phenotype in a depression mouse model. Conclusions Catecholamine‐induced neuroendocrine phenotypes of GC cells led to depression‐accelerated GC invasion and metastasis via the β2‐AR/MACC1 axis, while β2‐AR antagonist or MACC1 silencing could reverse it, showing promising potential therapeutic strategies for improving the outcome of GC patients with comorbid depression.

Dexmedetomidine is a very useful anesthetic, and it currently has less improvement in early childhood surgery. In order to study the effect of dexmedetomidine in improving the complex congenital heart surgery in infants and young children, this paper used machine learning algorithm to improve the image, and combined MRI (Magnetic Resonance Imaging) images for diagnostic analysis. At the same time, this paper collected experimental data to carry out algorithm analysis, collected cases to design experiments, used the method proposed in this paper to conduct research, and recorded the research results. Through comparative analysis, the algorithm proposed in this study has certain effects. Moreover, it has been proved that the dexmedetomidine infants have complicated effects in complex anesthesia surgery and can provide theoretical reference for subsequent related research.

Hyperhomocysteinemia (HHcy) induced endothelial dysfunction is associated with disturbance in circulating endothelial progenitor cells (EPCs). Nevertheless, whether this unfavorable effect of HHcy on circulating EPCs also exists in premenopausal women is still unknown. Therefore, this leaves an area for the investigation of the difference on the number and activity of circulating EPCs in premenopausal women with hyperhomocysteinemia and its underlying mechanism. The number of circulating EPCs was measured by fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining. The migration and proliferation of circulating were evaluated by the Transwell chamber assay and MTT. Additionally, the endothelial function and levels of nitric oxide (NO), VEGF, and GM-CSF in plasma and culture medium were determined. The number or activity of circulating EPCs and flow-mediated dilatation (FMD) in premenopausal women with or without HHcy were higher than those in postmenopausal women. However, no significant effect of HHcy on the number or activity of circulating EPCs in premenopausal women was observed. A similar alteration in NO level between the four groups was observed. There was a correlation between FMD and the number or activity of EPCs, as well as NO level in plasma or secretion by EPCs. For the first time, our findings illuminated the quantitive or qualitative alterations of circulating EPCs and endothelial function in premenopausal patients with HHcy are preserved, which was associated with retained NO production. The recuperated endothelial repair capacity is possibly the potential mechanism interpreting cardiovascular protection in premenopausal women with HHcy.

Background Severe community-acquired pneumonia (SCAP) is a critical disorder with high morbidity and mortality, usually manifested as acute respiratory failure and septic shock generally caused by exaggerated systemic inflammation. Interleukin-32 (IL-32), a pro-inflammatory cytokine, has been reported involved in various infectious diseases. We investigated the efficacy of the plasma IL-32 as a biomarker for evaluating the severity and clinical outcomes in SCAP patients. Methods A total of 124 adult immunocompetent SCAP patients and 87 healthy controls were enrolled in this observational, prospective cohort study. Results We found that PBMCs IL-32 mRNA and plasma IL-32 concentrations on admission of SCAP patients were significantly higher than healthy controls. Plasma IL-32 concentrations closely correlated with increasing severity scores, the need for vasopressor support or invasive mechanical ventilation but not with the etiology. The area under the curve (AUC) for predicting 30-day mortality using IL-32 was 0.812, is superior to WBCs and CRP. Incorporation of IL-32 with the severity scores were shown to improve the prognostic accuracy considerably. Furthermore, the 30-day cumulative survival rate in high IL-32 concentration group was significantly lower than that in the low concentration group. In a multivariate Cox regression analysis, higher IL-32 concentration and higher PSI score were recognized as the independent risk factors for survival, and the relative risks were 2.568 and 3.362, respectively. Conclusions Admission IL-32 concentration closely related to the severity and mortality of SCAP, and it may be served as a potential biomarker to help clinical judgment and management.

The dimensional instability and inferior mechanical strength of radiata pine (Pinus radiata D. Don) limit its use in musical instruments. To improve its properties, a two-step treatment by furfuryl alcohol (FA) and tung oil (TO) were used involving impregnation of FA precursor solution into the wood matrix, forming a highly cross-linked resin, followed by a modification with TO. Examination using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy revealed that FA resin was attached in cell walls and lumens, and the solidified TO in cell lumens and occluded pits. The incorporation of FA resin reduced the wood swelling coefficient by over 70% and the hydrophobic solidified TO decreased wood water uptake by over 80% enhancing wood dimensional stability. Although FA resin improved the modulus of elasticity and hardness of the wood, the modulus of rupture and impact bending strength were reduced. However, the additional TO impregnation step improved the modulus of rupture, impact bending strength, and wear resistance of the furfurylated wood. The performance of FA and TO treated radiata pine wood was better than that treated with FA or TO alone, and could meet the performance requirements of wood used for fretboard of string instruments.

The heterogeneity in prognoses and chemotherapeutic responses of colon cancer patients with similar clinical features emphasized the necessity for new biomarkers that help to improve the survival prediction and tailor therapies more rationally and precisely. In the present study, we established a stroma‐related lncRNA signature (SLS) based on 52 lncRNAs to comprehensively predict clinical outcome. The SLS model could not only distinguish patients with different recurrence and mortality risks through univariate analysis, but also served as an independent factor for relapse‐free and overall survival. Compared with the conventionally used TNM stage system, the SLS model clearly possessed higher predictive accuracy. Moreover, the SLS model also effectively screened chemotherapy‐responsive patients, as only patients in the low‐SLS group could benefit from adjuvant chemotherapy. The following cell infiltration and competing endogenous RNA (ceRNA) network functional analyses further confirmed the association between the SLS model and stromal activation‐related biological processes. Additionally, this study also identified three phenotypically distinct colon cancer subtypes that varied in clinical outcome and chemotherapy benefits. In conclusion, our SLS model may be a significant determinant of survival and chemotherapeutic decision‐making in colon cancer and may have a strong clinical transformation value.

Background Atherosclerosis, the underlying cause of the majority of cardiovascular diseases, is a lipid-driven, inflammatory disease of the large arteries. Atherosclerotic cardiovascular disease (ASCVD) threatens human lives due to high morbidity and mortality. Many studies have demonstrated that atherosclerosis is accelerated via activation of the NLRP3 inflammasome. The NLRP3 inflammasome plays a critical role in the development of vascular inflammation and atherosclerosis. In atherosclerotic plaques, excessive generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome. 13-Methylberberine (13-MB) is a newly synthesized compound used in traditional Chinese medicine that has outstanding antibacterial, antitumor, and antiobesity activities, especially anti-inflammatory activity. However, the role of 13-MB in atherosclerosis needs to be explored. Methods CCK-8 assays and flow cytometry were conducted to determine the cell viability and apoptotic profiles of human umbilical vein endothelial cells (HUVECs) treated with 13-MB. Carboxy-DCFH-DA and JC-10 assays were used to measure ROS and determine mitochondrial membrane potential. Western blot analysis was performed to investigate proteins that are associated with the NLRP3 inflammasome and autophagy. ELISA was used to detect and quantify inflammatory cytokines related to the NLRP3 inflammasome. Transfection and confocal microscopy were conducted to observe autophagy. Results Pretreatment with 13-MB markedly reduced cytotoxicity and apoptosis, as well as intracellular ROS production, in H2O2-induced HUVECs. Moreover, 13-MB showed a protective effect in maintaining mitochondrial membrane potential. 13-MB also suppressed NLRP3 inflammasome activation and promoted autophagy induction in HUVECs. Conclusion 13-MB exerts cytoprotective effects in an H2O2-induced cell injury model by inhibiting NLRP3 inflammasome activation via autophagy induction in HUVECs. These anti-inflammatory and autophagy induction activities may provide valuable evidence for further investigating the potential role of 13-MB in atherosclerosis.

We report a non-antibody GLUT1 inhibitor probe NBDQ that is 30 times more sensitive than the traditional GLUT1 transportable tracer for cancer cell imaging and Warburg effect-based tumor detection. NBDQ reveals significant advantages in terms of tumor selectivity, fluorescence stability and in vivo biocompatibility in xenograft tumor imaging, including triple-negative breast cancer.

Metabolic stress usually occurs in rapidly growing gastric cancer (GC) when the energy demand exceeds the supply. Interestingly, cancer cells can somehow escape this stress. Some small Rho GTPases regulating cell migration can be activated by metabolic stress. DLC3 is a RhoA-specific GTPase-activating protein of unclear function in cancer. We hypothesized that it participated in metabolic stress escape. Methods: Metabolic stress in GC cells was induced by glucose deprivation, and DLC3 expression was detected. Based on the prognostic value, cell viability, motility and glycolysis were detected in DLC3 differently expressed GC cells in vitro and in vivo. DLC3 downstream targets were screened and verified. Chemotactic ability was evaluated to study DLC3 and its downstream signaling on metabolic stress escape. In addition, therapeutic strategies targeting DLC3 were explored. Results: DLC3 expression was lowered by metabolic stress in GC cells. DLC3 downregulation indicated poor cancer prognosis, and silencing DLC3 promoted GC cell proliferation and invasion. MACC1, an oncogene promoting GC growth and metastasis, was proved to be the downstream target of DLC3. Low DLC3 expression and high MACC1 expression indicated high recurrence rate after GC resection. DLC3 transcriptionally inhibited MACC1 expression via RhoA/JNK/AP-1 signaling, and subsequently suppressed GC cell glycolysis and survival under metabolic stress. The DLC3/MACC1 axis modulated the chemotaxis of GC cells from energy deficient area to glucose abundant area. Finally, lovastatin was found to be a promising therapeutic drug targeting the DLC3/MACC1 axis. Conclusions: The DLC3/MACC1 axis modulates GC glycolysis and chemotaxis to escape glucose deprivation. Lovastatin may inhibit GC by targeting the DLC3/MACC1 axis.

This study investigates the alteration in function and number of circulating endothelial progenitor cells (EPCs) in patients with aortic dissection (AD), compared with hypertensive patients, and its possible mechanism. Thirty-four patients with acute aortic dissection (AAD) and 20 patients with primary hypertension were involved. Flow cytometry analysis was performed to detect the number of CD34+/KDR+ cells, and acetylated low density lipoprotein (ac-LDL) and lectin fluorescent staining method was applied to test the number of cultured EPCs. In addition, EPC migration and proliferation were measured, and plasma interleukin 6 (IL-6) and interleukin 17 (IL-17) levels were investigated. The number of circulating EPCs in the AAD group was lower than that in the non-AD group, and the proliferation and migration of circulating EPCs in the AAD group were lower than that in the non-AD group. In addition, the number, proliferation, and migration of circulating EPCs were significantly inversely correlated with the aortic dissection detection risk score (ADD-RS). More importantly, increased plasma IL-6 and IL-17 level was found in the AAD group, and the two inflammatory factors were inversely associated with the function and number of circulating EPCs in the AAD group. We first demonstrated that the number and function of circulating EPCs are reduced in the AAD group, which may be partly related to upregulated plasma IL-6 and IL-17. Our study provides novel insight on the underlying mechanism and potential therapeutic target of AAD.

Meningioma (MEN) is a common central nervous system disease. Accumulating evidence indicated that long non-coding RNA maternally expressed gene 3 (MEG3) participated in the progression of MEN. However, the potential mechanisms of MEG3 in altering the aggressive phenotypes of MEN need further exploration. Levels of MEG3, microRNA (miR)-29c, and A-kinase anchor protein 12 (AKAP12) were determined using quantitative real-time Polymerase Chain Reaction (qRT-PCR) assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the relationship between miR-29c and MEG3 or AKAP12. The protein level of AKAP12 was detected by western blot. Moreover, cell-cycle arrest, migration, invasion, and proliferation were assessed by flow cytometry, wound healing, transwell assays, and CCK-8 assay, respectively. Levels of MEG3 and AKAP12 were downregulated, while miR-29c was effectively increased in MEN tissues and cell line. Mechanically, MEG3 was a sponge of miR-29c to regulate the expression of AKAP12. Functionally, increase of MEG3 diminished cell-cycle, migration, invasion, and proliferation in MEN cells, and reintroduction of miR-29c could eliminate these effects. In addition, AKAP12 depletion overturned the inhibitory effects of miR-29c absence on cell-cycle, migration, invasion, and proliferation in vitro. Also, AKAP12 was co-regulated by MEG3/miR-29c axis. MEG3 mediated the aggressive behaviors of MEN cells via miR-29c/AKAP12 axis, supporting that MEG3 served as a promising biomarker for the diagnosis and treatment of human MEN.

Out-of-hospital cardiac arrest (OHCA) due to drowning carries high morbidity and mortality. There are a few studies on drowning-related out-of-hospital cardiac arrest (OHCA), in which patients are followed from the scene to hospital discharge. This study aims to compare patient characteristics between the survival group and mortality group of OHCA due to drowning. OHCA due to drowning cases were selected from the North America Termination of Resuscitation Association database between 2011 and 2015. The retrospective analysis of epidemiological characteristics and clinical features of all OHCA patients were performed. Of the 17,094 OHCA cases in the registry, 54 cases of OHCA due to drowning were included in this study. Among the 54 OHCAs due to drowning, 7 (13.0%) survived, while 47 (87.0%) died. Compared to the mortality group, the survival group had a higher bystander witness rate (57.1% versus 17.0%, p < 0.05 ), higher asystole rate (42.9% versus 78.7%, p < 0.05 ), and higher mild therapeutic hypothermia rate (28.6% versus 2.1%, p < 0.05 ). In addition, a large proportion of survivors were children (71.4%) and males (71.4%). Survival among OHCA’s due to drowning was found to be improved with a higher bystander rate, higher asystole rate, and higher mild hypothermia rate. In addition, children and males comprised the majority of survivors.

Diabetic neuropathy (DNP) is the most common complication of diabetes mellitus affecting approximately 50% of diabetes patients. Studying the effect of potential drugs with antioxidant properties and minimal toxicities on neural cells may lead to the development of new and safe pharmacotherapy. Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, is a clinically used sedative also known to have neural protection effect. In the present study, we aimed to investigate the protective role of DEX in high glucose (HG)-induced neural injury and its potential miRNA-related mechanisms. Our results showed that DEX exerted neuroprotective effects during high glucose-induced damage to PC12 cells in a dose-dependent manner. DEX restored cell viability and repressed LDH, Caspase-3 activity, ROS production, and cell apoptosis in HG-treated PC12 cells. MiR-125b-5p was significantly up-regulated in PC12 cells upon HG treatment and it was demonstrated as an target for DEX. The neuroprotective effects of DEX on HG-induced cellular injury were reversed through miR-125b-5p overexpression, and vitamin D receptor (VDR) is a direct targeted of the miR-125b-5p. Together, our results indicate that DEX displays neuroprotective effects on PC-12 cells under high glucose through regulating miR-125b-5p/VDR axis. Our findings might raise the possibility of potential therapeutic application of DEX for managing diabetic neuropathy neural injuries.

To predict the hazard-induced risks of buildings and infrastructures and assess the losses caused by hazards, the fragility curve method is a common quantitative risk assessment procedure f...

The history, electrocardiogram, age, risk factors, troponin (HEART) and global registry of acute coronary events (GRACE) scoring systems are commonly used to risk stratify patients with chest pain. This study investigated the application of these scores in predicting the short-term risk of a major adverse cardiac event (MACE) in patients with chest. A total of 509 patients were analyzed. All patients were followed up for 30 days after visiting our emergency department. At 30 days post-admission, the primary outcome (MACE) was recorded in 92 patients (18.1%), 88 (95.6%) of whom had experienced an acute myocardial infarction. Thirty-seven (40.2%) of the patients with a MACE underwent percutaneous coronary intervention and six patients (6.5%) died. The HEART and GRACE scores were both significantly higher in patients who developed a MACE than in those without (P

It has been proven that vitamin D was decreased and function of circulating endothelial progenitor cells (EPCs) was injured in systemic lupus erythematosus (SLE) patients. However, the effect of vitamin D on the function of EPCs in vitro and its mechanism need further study. Therefore, we investigated whether vitamin D improved the function of EPCs in vitro. The peripheral blood mononuclear cells of the participants were isolated from SLE patients and control subjects and cultured to EPCs. After the EPCs were treated with vitamin D (1,25-(OH)2D3), we evaluated the number, migratory and proliferative activities, and nitric oxide (NO) production of EPCs in vitro and detected vascular endothelial function by flow-mediated dilatation (FMD). We found that vitamin D in a dose-dependent manner improved number and migratory and proliferative activities of EPCs from SLE patients. Additionally, vitamin D upregulated NO production from EPCs in vitro. A significant correlation between the FMD and plasma NO level was found. There was also a correlation between number, migration, and proliferation of EPCs and NO production. Thus, the present findings indicated that vitamin D improved the function of EPCs from SLE patients via NO secretion.

Green composite processing technology of wood fibers is an inevitable choice for global sustainable development. In this research, waste poplar powder with different particle sizes was used to prepare glue-free biocomposites with good mechanical and waterproof properties by hot-molding. The biocomposites made of larger size wood powder had better tensile strength (40.3 MPa) and the biocomposites made of smaller size wood powder had the greater bending strength (50.5 MPa). The thickness swelling rate of the biocomposites was only 4.26% after soaking in water for 24 h. The cross-section morphology of the biocomposites showed that the cell wall collapses enhanced the interfacial bonding. Chemical analysis showed that lignin repolymerized with cellulose and hemicellulose for the vitrification transition. In addition, the biocomposites with excellent mechanical properties had no formaldehyde release, which can replace the traditional density boards made of adhesives and applied as furniture materials and in line with the concept of cleaner production.

Background Long non-coding RNAs (lncRNAs) have emerged as important regulators of human cancers. However, the functional roles of lncRNAs and the mechanisms responsible for their aberrant expression in gastric cancer (GC) have not been well characterized. Methods In this study, we examined the expression of lncRNA UFC1 in GC by qRT-PCR and explored its correlation with clinicopathological parameters. In vitro cell functional assays and in vivo animal studies were performed to determine the roles of UFC1 in GC progression. Results UFC1 was elevated and predicted poorer prognosis in GC. UFC1 knockdown inhibited while UFC1 overexpression promoted GC cell proliferation, migration, and invasion. UFC1 bound to miR-498 to antagonize its tumor suppressive effect on Lin28b. Suppression of Lin28b by miR-498 could be rescued by UFC1 overexpression, whereas Lin28b overexpression partially rescued UFC1 knockdown-mediated inhibition of GC cell function. Lin28b expression was increased in GC and suggested a co-expression pattern with UFC1. Conclusions UFC1 has a promoting role in GC progression, at least in part, by acting as a miR-498 sponge and derepressing Lin28b expression, which would provide a novel biomarker for GC diagnosis and prognosis and offer a potential target for GC therapy. Electronic supplementary material The online version of this article (10.1186/s13046-018-0803-6) contains supplementary material, which is available to authorized users.

Background Gastric cancer is common in developing regions, and we hope to find out an economical but practical prognostic indicator. It was reported that pre-treatment peripheral neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as differentiation status, were associated with cancer progression. Hence, we introduced a novel combined Neutrophil/platelet/lymphocyte/differentiation Score (cNPLDS) to improve the prediction value of palliative chemotherapeutic response in advanced gastric cancer. Methods According to statistical sample size estimation, 136 primary diagnosed unresectable advanced ptaients were included for a retrospective study. The follow-up end-point was progression free survival (PFS) during the first-line palliative chemotherapy. Differentiation stratified patients into well, medium and poor groups by score 1 to 3, while patients with neither elevated NLR and PLR, only one elevated, or both elevated were of the combined NLR-PLR score (cNPS) 1 to 3, respectively. The cNPLDS was calculated by multiplying the tumor differentiation score and cNPS. Results Determined by the receiver operating characteristic (ROC) curve, the optimal cut-off points for NLR and PLR were 3.04 and 223. Through univariate analysis and survival analysis, poor differentiation, high NLR, high PLR, high cNPS, and high cNPLDS respectively indicated inferior PFS during the first-line palliative chemotherapy. Patients were furhter classified into low to high risk groups by cNPLDS. Groups of elevated NLR, PLR, cNPS, and cNPLDS showed lower disease control rate. Compared to other parameters, cNPLDS significantly improved the accuracy in predicing the first-progression. Conclusions This study indicates that the novel parameter cNPLDS is superior to NLR or PLR alone, or even cNPS, in predicting the first-line chemosensitivity in advanced gastric cancer.

Idiopathic pulmonary fibrosis (IPF) is a serious and deadly disease for which treatment options are limited. The recent approval of antifibrosis agent nintedanib represents one of the first therapeutic approaches for the treatment of IPF. Here, we report novel indolinone-based multikinase inhibitors that target angiogenesis and fibrosis pathways and may serve as potential therapeutics for IPF. KBP-7018 is a novel, tyrosine kinase-selective inhibitor with potent effects on three fibrotic kinases (c-KIT, PDGFR, and RET). The pharmacokinetics (PK) properties of KBP-7018 were favorable in mice, rats, and dogs. In a bleomycin (BLM)-induced mouse pulmonary fibrosis model, 10, 30, and 100 mg/kg daily doses (q.d.) of KBP-7018 improved the 28-day survival rate in a dose-dependent manner. The improved efficacy of KBP-7018 compared to nintedanib provided a certain level of chemical validation for the involvement of PDGFR, c-KIT, and RET in IPF. Thus, KBP-7018 represents a novel multikinase inhibitor with differentiated activity, highly enhanced selectivity, and acceptable PK profiles that will enter phase I clinical trials.

Liu, C.; Huang, Z., and Chen, W., 2017. A numerical study of a submerged horizontal heaving plate as a breakwater. Using a nonlinear numerical wave tank (NWT) based on potential flow, a submerged horizontal plate heaving in regular waves was simulated, and its performance as a breakwater was examined. The NWT is based on a Mixed Eulerian-Lagrangian formulation and a de-singularized boundary integral equation method. The viscous effect on the motion of the plate is estimated by a linear damping coefficient, and the natural frequency of the heaving plate is controlled by the system stiffness. Compared with a fixed submerged horizontal plate, our results showed that the heaving motion of the plate with a critical stiffness could reduce the wave-transmission coefficient to almost zero and effectively suppress the free and locked waves on the leeside of the plate. The new type of breakwater can be an ideal alternative for small marinas and recreational harbors.

ZFAS1 is a newly identified long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes mediate cellular communications in cancer by transmitting active molecules. The presence of ZFAS1 in the circulating exosomes and the roles of exosomal ZFAS1 in gastric cancer (GC) remains unknown. The aim of this study was to investigate the potential roles of exosomal ZFAS1 in GC. The expression of ZFAS1 was examined in the tumor tissues, serum samples, serum exosomes of GC patients and cell lines using qRT-PCR. The correlation between ZFAS1 expression and the clinicopathological characteristics was analyzed. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. The biological roles of ZFAS1 in GC cell growth and mobility were investigated using cell counting, cell colony formation, and transwell migration assay. The potential mechanism of ZFAS1 was demonstrated using flow cytometry, western blot, and qRT-PCR. ZFAS1 expression was elevated in GC cells, tumor tissues, serum and serum exosomes of GC patients. The increased ZFAS1 expression was significantly correlated with lymphatic metastasis and TNM stage. ZFAS1 knockdown inhibited the proliferation and migration of GC cells by suppressing cell cycle progression, inducing apoptosis, and inhibiting epithelial-mesenchymal transition (EMT). On the contrary, ZFAS1 overexpression promoted the proliferation and migration of GC cells. Moreover, ZFAS1 was present in exosomes and could be transmitted by exosomes to enhance GC cell proliferation and migration. ZFAS1 could be delivered by exosomes to promote GC progression, which suggests that ZFAS1 may serve as a potential diagnostic and prognostic biomarker for GC.

Two novel fluorescent bioprobes, namely, 6N-Gly-Cy3 and 6N-Gly-Cy5, were designed and synthesized for real-time glucose transport imaging as well as potentially useful tracer for galactokinase metabolism. The structure of the bioprobes was fully characterized by 1H NMR, 13C NMR, IR, and HRMS. The fluorescence properties, glucose transporter (GLUT) specificity, and the quenching and safety profiles were studied. The cellular uptake of both bioprobes was competitively diminished by d-glucose, 2-deoxy-d-glucose and GLUT specific inhibitor in a dose-dependent manner in human colon cancer cells (HT29). Comparison study results revealed that the 6N-derived bioprobes are more useful for real-time imaging of cell-based glucose uptake than the structurally similar fluorescent tracer 6-NBDG which was not applicable under physiological conditions. The up to 96 h long-lasting quenching property of 6N-Gly-Cy5 in HT29 suggested the potential applcability of the probe for cell labeling in xenograft transplantation as well as in vivo animal imaging studies.

In general, the stock prices of the same industry have a similar trend, but those of different industries do not. When investing in stocks of different industries, one should select the optimal model from lots of trading models for each industry because any model may not be suitable for capturing the stock trends of all industries. However, the study has not been carried out at present. In this paper, firstly we select 424 S&P 500 index component stocks (SPICS) and 185 CSI 300 index component stocks (CSICS) as the research objects from 2010 to 2017, divide them into 9 industries such as finance and energy respectively. Secondly, we apply 12 widely used machine learning algorithms to generate stock trading signals in different industries and execute the back-testing based on the trading signals. Thirdly, we use a non-parametric statistical test to evaluate whether there are significant differences among the trading performance evaluation indicators (PEI) of different models in the same industry. Finally, we propose a series of rules to select the optimal models for stock investment of every industry. The analytical results on SPICS and CSICS show that we can find the optimal trading models for each industry based on the statistical tests and the rules. Most importantly, the PEI of the best algorithms can be significantly better than that of the benchmark index and "Buy and Hold" strategy. Therefore, the algorithms can be used for making profits from industry stock trading.

Aiming at evaluating the reliability of the high-strength bolts’ fake tightened-up phenomena of the bolted spherical joints in a spatial grid structure, this research studied the tensile strength, stiffness, and failure modes of the bolted spherical joints with different bolt types and screwing depths using a combined method of the lab experiments and numerical simulations. A total of 40 axial tension tests of the bolted spherical joints were conducted with five different bolt types and eight different screwing depths. The test results showed that the bolted spherical joints with the different bolt screwing depths of high strength bolts suffered three failure modes, namely, the thread failure, bolt fracture failure, and sphere rupture failure. Validated by its feasibility and accuracy, the proposed numerical simulation method of the bolted spherical joints can estimate the ultimate strengths and failure modes, as well as the detailed stress distribution and failure development process. According to the test and numerical analysis results, a group of calculation formulas was developed for predicting the tensile strength of bolted spherical joints with different bolt screwing depths.

By applying conformational restrictions, we were able to discover highly potent 1,3-diaminopyrimidine based covalent inhibitors of BTK, such as 8a (IC50=3.76 nM), and providing useful information of its active conformation. We are developing these novel small molecule covalent inhibitors of BTK toward oral agents for Rheumatoid arthritis.

To investigate the effect of GRACE scores on prediction of 30-day cardiovascular adverse events in acute chest pain patients. A prospective, observational analysis was conducted in the patients with acute chest pain in Emergency Department (ED) from January 1, 2016 through January 1, 2017. Data including characteristics and GRACE scores were collected. All causes leading to MACE were followed up at 30th day after the onset of acute chest pain. Among a total of 600 patients presenting with acute chest pain enrolled in this study, 302 were male (50.3%) and 298 were female (49.7%). The range of age was 20-80 years old. During follow-up period, 102 patients had MACE, 498 patients had no MACE. When compared with non-MACE group, factors including number of Smoker, Hypercholesterolemia, Diabetes, Hypercholesterolemia and patients admitted in CCU as well as GRACE scores, were significantly higher in MACE group (P

Endothelial progenitor cells (EPCs) have endogenous endothelium-reparative potential, but obesity impairs EPCs. Overweight premenopausal women have a normal number of circulating EPCs with functional activity, but whether EPCs in overweight postmenopausal women can repair obesity-related endothelial damage requires further investigation. For this purpose, we examined the function and number of circulating EPCs, evaluated vascular endothelial function, and explored the underlying mechanism. Compared with normal weight or overweight age-matched men, postmenopausal women (overweight or normal weight) had a diminished number of circulating EPCs and impaired vascular endothelial function, as detected by flow-mediated dilatation. Moreover, GTCPH I expression and the nitric oxide level in overweight postmenopausal women and men were significantly decreased. Together, our findings demonstrate that the number or function of circulating EPCs and endothelial function, which is partially regulated by the GTCPH I/BH4 signaling pathway, is not preserved in overweight postmenopausal women. The GTCPH I/BH4 pathway in circulating EPCs may be a potential therapeutic target for endothelial injury in overweight postmenopausal women.

Objectives Long noncoding RNAs (lncRNAs) play important roles in cancer development and progression. The deregulated expression of LINC00978 has been reported in human cancers. However, the expression pattern and biological roles of LINC00978 in gastric cancer (GC) remain unclear. In this study, we investigated the potential roles and clinical value of LINC00978 in gastric cancer. Materials and methods QRT-PCR was performed to investigate the expression of LINC00978 in gastric cancer cell lines, tissues and serum samples. Cell counting, colony formation, transwell migration and matrigel invasion assays were performed to determine the effects of shRNA-mediated knockdown of LINC00978 on gastric cancer cell functions. In vivo tumour growth assay was also conducted. Flow cytometry, immunohistochemistry, western blot and qRT-PCR were used for potential mechanism study. Results LINC00978 expression level was elevated in GC tumour tissues, serum samples and cell lines. The expression level of LINC00978 was significantly correlated with tumour size (P = 0.02), lymphatic metastasis (P = 0.009) and TNM stage (P = 0.009). LINC00978 knockdown inhibited the proliferation of GC cells by suppressing cell cycle progression and inducing apoptosis. LINC00978 knockdown also inhibited the migration and invasion of GC cells. In addition, LINC00978 knockdown inhibited the activation of TGF-β/SMAD signalling pathway and the process of epithelial-mesenchymal transition (EMT) in GC cells. Moreover, the in vivo tumorigenicity of LINC00978 knockdown GC cells in mice was significantly decreased. Conclusions LINC00978 promotes gastric cancer progression and may serve as a potential biomarker for GC.

Zhenhua Huang,1 Heran Li,1 Qian Zhang,2 Xiaojuan Tan,2 Fangzheng Lu,1 Hongzhuo Liu,1 Sanming Li11School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2KBP BioSciences Co. Ltd., Jinan, Shandong, People’s Republic of ChinaAbstract: KBP-7018 is a novel selective tyrosine kinase inhibitor with potential for the treatment of idiopathic pulmonary fibrosis. The objective of this study was to characterize the preclinical pharmacokinetics of KBP-7018 in vitro and in vivo, and then to assess the likelihood of developing KBP-7018 as a clinical candidate. The systemic clearance (CL) of KBP-7018 was relatively low in rodents and monkeys with a value of less than 30% of hepatic blood flow, while it was high in dogs. The steady-state volume of distribution (Vss) ranged from 1.51L/kg to 4.65L/kg across the species tested. The maximum concentration (Cmax) of KBP-7018 occurred at 0.25–6hours after oral dosing, and the bioavailability was moderate (21%–68%). The human CL (~20% of hepatic blood flow) and Vss (1.6–5.3L/kg) were predicted by allometric scaling method and together with the other modeling methods indicated low metabolism and acceptable half-time (4.8–19.3hours) in vivo. Overall, the preclinical data make it amenable to further oral solid dosage from design for the upcoming Phase I trials in human.Keywords: idiopathic pulmonary fibrosis, tyrosine kinase inhibitor, pharmacokinetics, KBP-7018

Radiofrequency ablation has become an increasingly common therapeutic technique for patients with hepatocellular carcinoma or metastatic liver tumors. However, reports on the effect of percutaneous radiofrequency ablation (PRFA) on circulating tumor cells (CTCs) are limited. The present study aimed to further investigate the impacts of PRFA on the numbers and phenotypes of CTCs in patients with hepatocellular carcinoma or metastatic liver tumors. A total of 43 patients with hepatocellular carcinoma or 7 types of metastatic liver tumors were treated with PRFA. A total of 5 ml blood per sample were collected from the peripheral circulation 30 min before and 3 days after PRFA. The total number of CTCs significantly increased 3 days after PRFA, and the mesenchymal phenotype CTCs, which also increased significantly, significantly contributed to the overall increase in CTCs. Furthermore, the lymphocyte levels were significantly decreased following PRFA, and the CTC level was significantly higher in patients with decreased lymphocyte levels compared with those with increased lymphocyte levels. Liver tumor PRFA may increase the level of mesenchymal phenotype CTCs, which is significantly associated with the lymphocyte count. Factors pertaining to the performance of PRFA were also investigated in the present research, but no significant results were identified.

Long noncoding RNAs (LncRNAs) play important roles in tumor development and progression. The expression of lncRNAs is frequently dysregulated in human cancer. DANCR (anti-differentiation noncoding RNA) is a newly identified lncRNA in human cancer, however, its functional roles and clinical value in gastric cancer (GC) remains unknown. In this study, we investigated the expression of DANCR in the tumor tissues and serum of GC patients and analyzed the correlation between DANCR expression levels and the clinicopathological characteristics. Our results showed that the expression of DANCR was higher in the tumor tissues than that in the adjacent non-cancerous tissues. The expression level of DANCR was also elevated in the serum of GC patients compared to that of healthy controls. The expression levels of DANCR were significantly associated with tumor size, TNM stage, lymphatic metastasis and invasion depth. DANCR knockdown inhibited the proliferation of GC cells by inducing cell cycle arrest and cell apoptosis. In addition, DANCR knockdown suppressed gastric cancer growth in vivo. Moreover, DANCR knockdown inhibited the migration and invasion of GC cells via the suppression of epithelial-mesenchymal transition (EMT). However, DANCR overexpression had the opposite effect. DANCR is activated by SALL4 in gastric cancer cells and exerted its oncogenic activities through the activation of β-catenin pathway. Taken together, our findings suggest that DANCR promotes the progression of gastric cancer and have the potential to serve as a novel diagnostic biomarker.

Excess intracellular reactive oxygen species (ROS) beyond a threshold can induce apoptosis in cancer cells. However, the signal pathways that can augment the proapoptotic function of ROS remain largely unknown. We previously identified a tumor suppressor, alpha-tocopherol-associated protein (TAP), yet little is known regarding the role of TAP in the apoptotic signaling in prostate cancer. Interestingly, we recently found that exposure of prostate cancer cells to hydrogen peroxide (H(2)O(2) ) resulted in induced apoptosis as well as increased expression of TAP. Small interfering RNA (siRNA) mediated silencing of endogenous TAP expression conferred effective protection from H(2)O(2) -induced apoptosis. Further mechanistic study showed exposure of prostate cancer cells to H(2)O(2) resulted in increased phosphorylation of both JNK and c-Jun, and TAP siRNA effectively decreased H(2)O(2) -induced JNK and c-Jun phosphorylation. Immunoprecipitation experiments revealed that JNK physically associates with TAP. Furthermore, signaling downstream of JNK to the AP-1 complex and BH-3-only subfamily were found to be regulated on changing the TAP expression status. TAP could also promote the oxidative stress-induced apoptosis effect of docetaxel. In the mice xenograft model, H(2)O(2) treatment induced TAP expression, JNK phosphorylation and apoptosis of prostate cancer. Recombinant adeno-associated virus 2 (rAAV2)-TAP injection significantly sensitizes this H(2)O(2) proapoptotic effect. Together, we have identified a novel functional mechanism that the cross-talk of TAP-JNK is involved in oxidative stress-induced apoptosis in prostate cancer cells. Disrupting the redox balance of cancer cells by this signaling may enable therapeutic selectivity and provide benefit to overcome the drug resistance of prostate cancer.

Androgens initiate a complex network of signals within the UGS that trigger prostate lineage commitment and bud formation. Given its contributions to organogenesis in other systems, we investigated a role for canonical Wnt signaling in prostate development. We developed a new method to achieve complete deletion of beta-catenin, the transcriptional coactivator required for canonical Wnt signaling, in early prostate development. Beta-catenin deletion abrogated canonical Wnt signaling and yielded prostate rudiments that exhibited dramatically decreased budding and failed to adopt prostatic identity. This requirement for canonical Wnt signaling was limited to a brief critical period during the initial molecular phase of prostate identity specification. Deletion of beta-catenin in the adult prostate did not significantly affect organ homeostasis. Collectively, these data establish that beta-catenin and Wnt signaling play key roles in prostate lineage specification and bud outgrowth.

Vascular dementia (VaD) is one of common causes of dementia following Alzheimer's disease. However, up to date, there has been no effective treatment for VaD yet. Cellular therapy with mesenchymal stem cells (MSCs) and some extract ingredients of traditional Chinese medicines are expected to improve learning and memory function in VaD model. In this study, we applied tanshinone II A (TSA) and MSCs in the rat model of VaD to evaluate the synergistic effect of TSA and MSCs on preventing cognitive deficits as well as explore the underlying mechanism. The VaD model was established by using modified four-vessel occlusion(4-VO) on rats. Our results showed that TSA combined with MSCs treatment provided a better protecting effect on spatial learning and memory function in the VaD rats than those treated with either MSCs or TSA only. The combined administration of TSA and MSCs demonstrated a synergistic effect on suppressing neuronal apoptosis in the hippocampus, attenuating tau phosphorylation and enhancing the activity of central cholinergic system. These results indicated that the combination of TSA and MSCs exhibits better therapeutic effects on learning and memory protection than the treatment with either MSCs or TSA only, suggesting a potential novel treatment for VaD.

Novel cis-2-methylmalonato(trans-R,R-cyclohexane-1,2-diamine)platinum(II) glycoconjugates derived from different sugar motifs, namely, glucose (Glu-Me-Pt), mannose (Man-Me-Pt) and galactose (Gal-Me-Pt) were designed and synthesized based on the third generation clinical drug oxaliplatin for potential glucose transporters (GLUTs) mediated tumor targeting. All platinum(II) glycoconjugates were characterized by 1H NMR, 13C NMR, IR, HRMS as well as 195Pt-NMR analysis. Despite their substantial improvement in water solubility, the conjugates exhibited comparable or better in vitro cytotoxicities than oxaliplatin determined in six different human cancer cell lines. Glu-Me-Pt has been shown to be more effective than cisplatin and oxaliplatin with improved therapeutic index in leukemia-bearing DBA/2 mice model. The potential GLUT transportability of the complexes was investigated using cell-based fluorescent competition assay and GLUT inhibitor mediated cell viability analysis in GLUT over-expressing HT29 cell line. Each sugar motif was found to be useful to enable the platinum(II) complexes as substrate for GLUT mediated cell uptake. In vitro DNA adduct formation analysis has been investigated for the first time for this class of compounds to reveal the intrinsic differences in antitumor activity between the malonatoplatinum(II) glycoconjugates and oxaliplatin. The intrinsic DNA reactivity of the platinum(II)-sugar conjugates was found as Gal-Me-Pt > Glu-Me-Pt > Man-Me-Pt ≈ oxaliplatin by kinetic study on the formation of platinum(II) adducts with guanosine-5′-monophosphate (5′-GMP). The results from this study demonstrate the usefulness of glucose, mannose and galactose as alternative sugar motif on glycoconjugation for GLUT mediated drug design and pharmaceutical R&D, and the obtained fundamental results also support the potential of the GLUT targeted platinum(II)-sugar conjugates as lead compounds for further pre-clinical evaluation.

Background Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Methods Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5–8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Results Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Conclusions Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer. Electronic supplementary material The online version of this article (doi:10.1186/s12944-016-0212-9) contains supplementary material, which is available to authorized users.

Zhenhua Huang 1,2,3 , Paula J Hurley 1 , Brian W Simons 1,2,3 , Luigi Marchionni 2,3 , David M Berman 1,2,3 , Ashley E Ross 1 and Edward M Schaeffer 1,2,3 1 Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 2 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 3 Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Received: June 26, 2012; Accepted: June 30, 2012; Published: July 2, 2012; Keywords: Sox9, prostate, development, cancer, initiation Correspondence: Edward M Schaeffer, email: // // Abstract Prostate cancer is one of the most common malignancies and the second leading cause of death from cancer in men. The molecular mechanisms driving prostate carcinogenesis are complex; with several lines of evidence suggesting that the re-expression of conserved developmental programs plays a key role. In this study, we used conditional gene targeting and organ grafting, to describe conserved roles for the transcription factor Sox9 in the initiation of both prostate organogenesis and prostate carcinogenesis in murine models. Abrogation of Sox9 expression prior to the initiation of androgen signaling blocks the initiation of prostate development. Similarly, Sox9 deletion in two genetic models of prostate cancer (TRAMP and Hi-Myc) prevented cancer initiation. Expression profiling of Sox9-null prostate epithelial cells revealed that the role of Sox9 in the initiation of prostate development may relate to its regulation of multiple cytokeratins and cell adherence/polarity. Due to its essential role in cancer initiation, manipulation of Sox9 targets in at-risk men may prove useful in the chemoprevention of prostate cancer.

In this study, solitary wave interaction with emergent, rigid vegetation was studied numerically and experimentally. Laboratory experiments were carried out in a wave flume with vegetation models of different lengths and porosities; the Boussinesq equations with the effects of the vegetation being modeled by a quadratic drag law are used to simulate the wave scattering by and the wave propagation through vegetation. Effects of incident wave height, vegetation density, and vegetation length are discussed. An empirical expression for the mean drag coefficient of emergent, rigid vegetation is presented and compared with other available data. The results are useful for studying tsunami hazard mitigation by coastal forests.

The influence of linear elastic support on the damper effectiveness of a cable-damper system was investigated by modeling the system as a taut string, an intermediate damper, and a spring in series. Two types of damper were analyzed in this study: (1) the linear elastic damper; and (2) the friction threshold. An exact formulation for the free vibration of the system was developed for the linear viscous damping system, and a complex eigenfrequencies equation was worked to obtain the explicit solution for the frequency shift. A damping ratio equation for different modes, which depicts the effect of the spring, was developed from the frequency shift. An effective flexibility coefficient was introduced to investigate the effect of different values of support stiffness on the effectiveness of the linear viscous damper. A universal curve family diagram was constructed, which indicated that linear elastic support reduces the effectiveness of the linear viscous damper. The universal curve obtained previously by Main and Jones was a special case of this universal curve family for the case in which the stiffness of the support approached infinity. The equation of maximum force introduced to the spring was also derived and was shown to be positively related to the cable tension force and the cable vibration amplitude at the damper attachment location. The influence of the linear elastic support on a cable-damper system with a friction threshold was also investigated by using the result of the linear viscous damper and the equivalent energy method. The result showed that the linear elastic support also reduces the effectiveness of the friction threshold. An equation showing how to select an optimal friction threshold for a stay cable was also proposed.

A point-of-care testing (POCT) for troponin I (TnI) in the Emergency Department (ED) was compared to a high-sensitivity TnT (hs-TnT) in the central laboratory (CLT) to determine the influences of test system on the diagnostic performance, stay time and medical cost in ED in patients with non-ST