Application of social vulnerability indicators to climate change for the southwest coastal areas of Taiwan

The impact of climate change on the coastal zones of Taiwan not only affects the marine environment, ecology, and human communities whose economies rely heavily on marine activities, but also the sustainable development of national economics. The southwest coast is known as the area most vulnerable to climate change; therefore, this study aims to develop indicators to assess social vulnerability in this area of Taiwan using the three dimensions of susceptibility, resistance, and resilience. The modified Delphi method was used to develop nine criteria and 26 indexes in the evaluation, and the analytic hierarchy process method was employed to evaluate the weight of each indicator based on the perspectives of experts collected through questionnaire surveys. The results provide important information pertaining to the vulnerability of the most susceptive regions, the lowest-resistance areas, and the least resilient townships on the southwest coast. The most socially vulnerable areas are plotted based on the present analysis. Experts can consider the vulnerability map provided here when developing adaptation policies. It should be kept in mind that improving the capacities of resistance and resilience is more important than reducing susceptibility in Taiwan

Protective effects of Scoparia dulcis L. extract on high glucose-induced injury in human retinal pigment epithelial cells

Diabetic retinopathy (DR) is a major cause of vision loss in diabetic patients. Hyperglycemia-induced oxidative stress and the accumulation of inflammatory factors result in blood-retinal barrier dysfunction and the pathogenesis of DR. Scoparia dulcis L. extract (SDE), a traditional Chinese medicine, has been recently recognized for its various pharmacological effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory, and anti-oxidative activities. However, there is no relevant research on the protective effect of SDE in DR. In this study, we treated high glucose (50 mM) in human retinal epithelial cells (ARPE-19) with different concentrations of SDE and analyzed cell viability, apoptosis, and ROS production. Moreover, we analyzed the expression of Akt, Nrf2, catalase, and HO-1, which showed that SDE dose-dependently reduced ROS production and attenuated ARPE-19 cell apoptosis in a high-glucose environment. Briefly, we demonstrated that SDE exhibited an anti-oxidative and anti-inflammatory ability in protecting retinal cells from high-glucose (HG) treatment. Moreover, we also investigated the involvement of the Akt/Nrf2/HO-1 pathway in SDE-mediated protective effects. The results suggest SDE as a nutritional supplement that could benefit patients with DR

A Combined DNA-Affinic Molecule and N-Mustard Alkylating Agent Has an Anti-Cancer Effect and Induces Autophagy in Oral Cancer Cells

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC50 in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future

Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

<p>Abstract</p> <p>Background</p> <p>A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.</p> <p>Methods</p> <p>Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.</p> <p>Results</p> <p>A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α <it>in vitro </it>was through a <it>ras</it>- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (<it>p </it>< 0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (<it>p </it>< 0.01).</p> <p>Conclusions</p> <p>In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.</p

Piercing and surface-crack defects in combination extrusion of fasteners

Piercing or surface-crack defect occurs in combination-extruding the support pin. There has been so far insufficient knowledge in avoiding such forming defects in forming the similar products. In this paper, a combination-extrusion experiment, with various combinations of forward and backward extrusion ratios, was conducted to observe the occurrence of the defects. The result shows that the defects occur at low level of both forward extrusion ratio and backward extrusion ratio used in the combination-extrusion process. The low forming level causes the onset of insufficient plastic metal-flow, which is similar to that of inhomogeneous deformation in the unidirectional extrusion or drawing process. A forming limit diagram was constructed and can be used in the defect prediction for the future development of similar products

Piercing and surface-crack defects in combination extrusion of fasteners

Piercing or surface-crack defect occurs in combination-extruding the support pin. There has been so far insufficient knowledge in avoiding such forming defects in forming the similar products. In this paper, a combination-extrusion experiment, with various combinations of forward and backward extrusion ratios, was conducted to observe the occurrence of the defects. The result shows that the defects occur at low level of both forward extrusion ratio and backward extrusion ratio used in the combination-extrusion process. The low forming level causes the onset of insufficient plastic metal-flow, which is similar to that of inhomogeneous deformation in the unidirectional extrusion or drawing process. A forming limit diagram was constructed and can be used in the defect prediction for the future development of similar products

Investigating sphingolipids as biomarkers for the outcomes of acute ischemic stroke patients receiving endovascular treatment

Background: Long-chain ceramides are associated with the mechanisms and clinical outcomes of acute ischemic stroke (AIS). This study aimed to investigate the plasma ceramides and sphingosine-1-phosphate in AIS patients undergoing endovascular thrombectomy (EVT) and their associations with outcomes. Methods: Plasma samples were collected from 75 AIS patients who underwent EVT before (T1), immediately after (T2), and 24 h after (T3) the procedures and 19 controls that were matched with age, sex, and co-morbidities. The levels of ceramides with different fatty acyl chain lengths and sphingosine-1-phosphate were measured by UHPLC–ESI–MS/MS. A poor outcome was defined as a modified Rankin Scale score of 3–6 at 3 months after stroke. Results: The plasma levels of long-chain ceramides Cer (d18:1/16:0) at all three time points, Cer (d18:1/18:0) at T1 and T3, and Cer (d18:1/20:0) at T1 and very-long-chain ceramide Cer (d18:1/24:1) at T1 were significantly higher in AIS patients than those in the controls. In contrast, the plasma levels of sphingosine-1-phosphate in AIS patients were significantly lower than those in the controls at all three time points. Among the AIS patients, 34 (45.3%) had poor functional outcomes at 3 months poststroke. Multivariable analysis showed that higher levels of Cer (d18:1/16:0) and Cer (d18:1/18:0) at all three time points, Cer (d18:1/20:0) at T1 and T2, and Cer (d18:1/24:0) at T2 remained significantly associated with poor functional outcomes after adjustment for potential confounding factors. Conclusion: Plasma ceramides were elevated early in AIS patients with acute large artery occlusion. Furthermore, Cer (d18:1/16:0) and Cer (d18:1/18:0) could be early prognostic indicators for AIS patients undergoing EVT

Quantification of Gut Microbiota Dysbiosis-Related Organic Acids in Human Urine Using LC-MS/MS

Urine organic acid contains water-soluble metabolites and/or metabolites—derived from sugars, amino acids, lipids, vitamins, and drugs—which can reveal a human’s physiological condition. These urine organic acids—hippuric acid, benzoic acid, phenylacetic acid, phenylpropionic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyl acetic acid, 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenyl propionic acid, and 3-indoleacetic acid—were the eligible candidates for the dysbiosis of gut microbiota. The aim of this proposal was to develop and to validate a liquid chromatography–tandem mass spectrometry (LC-MS/MS) bioanalysis method for the nine organic acids in human urine. Stable-labeled isotope standard (creatinine-d3) and acetonitrile were added to the urine sample. The supernatant was diluted with deionized water and injected into LC-MS/MS. This method was validated with high selectivity for the urine sample, a low limit of quantification (10–40 ng/mL), good linearity (r > 0.995), high accuracy (85.8–109.7%), and high precision (1.4–13.3%). This method simultaneously analyzed creatinine in urine, which calibrates metabolic rate between different individuals. Validation has been completed for this method; as such, it could possibly be applied to the study of gut microbiota clinically

Dinitrile–Mononitrile-Based Electrolyte System for Lithium-Ion Battery Application with the Mechanism of Reductive Decomposition of Mononitriles

The development of electrolytes capable of performing at a high voltage (>5 V) is essential for the advancement of lithium-ion batteries. In the present work, we have investigated a dinitrile–mononitrile-based electrolyte system that can offer electrochemical stability up to 5.5 V at room temperature. The electrolytes consist of 1.0 M lithium bis­(trifluoromethane)­sulfonamide in various volume proportions of glutaronitrile, a dinitrile, and butyronitrile, a mononitrile (10/0; 8/2; 6/4; 4/6; 2/8; 10/0). The ionic conductivity of the electrolytes was found to be 3.1 × 10^–3–10.6 × 10^–3 S cm^–1 at 30 °C, comparable with commercially used carbonate-based electrolytes. However, butyronitrile reacts with Li metal to give 3-amino-2-ethylhex-2-ene-nitrile, 2,6-dipropyl-5-ethylpyrimidin-4-amine, and oligomers/polymers. These compounds have been characterized by nuclear magnetic resonance techniques, and based on these findings, a plausible mechanism of reactivity of mononitriles toward Li metal has been proposed. Finally, 5 wt % of vinylene carbonate is added to the glutaronitrile/butyronitrile (6/4 ratio) system to inhibit the reductive decomposition of butyronitrile. The resultant electrolyte system is used in the assembly of several coin cells consisting of a LiFePO₄ composite cathode and a Li metal anode. The cells perform up to 3 C charge/discharge rate with reasonably good discharge capacity and also display a cycle life of more than 100 cycles at a 0.5 C rate with capacity retention above 95% at room temperature