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This paper deeply investigated the gate leakage and dielectric breakdown mechanisms of the Normally-OFF GaN MOSFET with LPCVD-SiNx/PEALD-AlN dual Gate Dielectric and in-situ H2(15%)/N2(85%) plasma pretreatment. The in-situ plasma pretreatment was performed in a PEALD system prior to the PEALD-AlN deposition. Experimental studies showed that the in-situ H2(15%)/N2(85%) plasma pretreatment is effective in improving the quality of the AlN/GaN interface, the LPCVD-SiNx/PEALD-AlN dual Gate Dielectric exhibits not only high breakdown electric field but low leakage current. Experiments have proved dominant mechanism of the leakage current through LPCVD-SiNx/PEALD-AlN Gate Dielectric is identified to be Poole-Frenkel emission at low fields and Fowler-Nordheim tunneling at high fields. Further, gate dielectric time-dependent dielectric breakdown of electric-field-accelerated and temperature-accelerated was investigated.

Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with the recurrence of bladder cancer. Previous studies have shown that activation of FGFR and HER2 signaling are involved in bladder cancer cell proliferation and drug resistance. Smoking is the most common etiologic risk factor for bladder cancer, and there is emerging evidence that smoking is associated with cisplatin resistance. However, the underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes. Our previous studies have shown that acrolein contributes to bladder carcinogenesis through the induction of DNA damage and inhibition of DNA repair. In this study, we found that acrolein induced cisplatin resistance and tumor progression in both non–muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) cell lines RT4 and T24, respectively. Activation of HER2 and FGFR3 signaling contributes to acrolein-induced cisplatin resistance in RT4 and T24 cells, respectively. Furthermore, trastuzumab, an anti-HER2 antibody, and PD173074, an FGFR inhibitor, reversed cisplatin resistance in RT4 and T24 cells, respectively. Using a xenograft mouse model with acrolein-induced cisplatin-resistant T24 clones, we found that cisplatin combined with PD173074 significantly reduced tumor size compared with cisplatin alone. These results indicate that differential molecular alterations behind cisplatin resistance in NMIBC and MIBC significantly alter the effectiveness of targeted therapy combined with chemotherapy. This study provides valuable insights into therapeutic strategies for cisplatin-resistant bladder cancer.

Supplementary Figure from Cigarette Smoke Containing Acrolein Contributes to Cisplatin Resistance in Human Bladder Cancers through the Regulation of HER2 Pathway or FGFR3 Pathway

A metal-oxide-semiconductor high-electron-mobility transistor (MOS-HEMT) is proposed based on using a Al2O3/ZrO2 stacked layer on conventional AlGaN/GaN HEMT to suppress the gate leakage current, decrease flicker noise, increase high-frequency performance, improve power performance, and enhance the stability after thermal stress or time stress. The MOS-HEMT has a maximum drain current density of 847 mA/mm and peak transconductance of 181 mS/mm. The corresponding subthreshold swing and on/off ratio are 95 mV/dec and 3.3 × 107. The gate leakage current can be reduced by three orders of magnitude due to the Al2O3/ZrO2 stacked layer, which also contributes to the lower flicker noise. The temperature-dependent degradation of drain current density is 26%, which is smaller than the 47% of reference HEMT. The variation of subthreshold characteristics caused by thermal or time stress is smaller than that of the reference case, showing the proposed Al2O3/ZrO2 stacked gate dielectrics are reliable for device applications.

The ability to observe biological nanostructures forms a vital step in understanding their functions. Thanks to the invention of expansion microscopy (ExM) technology, super-resolution features of biological samples can now be easily visualized with conventional light microscopies. However, when the sample is physically expanded, the demand for deep and precise 3D imaging increases. Lattice lightsheet microscopy (LLSM), which utilizes a planar illumination that is confined within the imaging depth of high numerical aperture (NA=1.1) detection objective, fulfils such requirements. In addition, optical tiling could be implemented to increase the field of view (FoV) by moving the lightsheet without mechanically moving the samples or the objective for high-precision 3D imaging. In this review article, we will explain the principle of the tiling lattice lightsheet microscopy (tLLSM), which combines optical tiling and lattice lightsheet, and discuss the applications of tLLSM in ExM.

A metal-oxide-semiconductor high-electron-mobility transistor (MOS-HEMT) is proposed based on using a Al

Purpose: We aimed to establish the transcriptome diagnostic signature of postmenopausal osteoporosis (PMOP) to identify diagnostic biomarkers and score patient risk to prevent and treat PMOP.Methods: Peripheral blood mononuclear cell (PBMC) expression data from PMOP patients were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using the “limma” package. The “WGCNA” package was used for a weighted gene co-expression network analysis to identify the gene modules associated with bone mineral density (BMD). Least absolute shrinkage and selection operator (LASSO) regression was used to construct a diagnostic signature, and its predictive ability was verified in the discovery cohort. The diagnostic values of potential biomarkers were evaluated by receiver operating characteristic curve (ROC) and coefficient analysis. Network pharmacology was used to predict the candidate therapeutic molecules. PBMCs from 14 postmenopausal women with normal BMD and 14 with low BMD were collected, and RNA was extracted for RT-qPCR validation.Results: We screened 2420 differentially expressed genes (DEGs) from the pilot cohort, and WGCNA showed that the blue module was most closely related to BMD. Based on the genes in the blue module, we constructed a diagnostic signature with 15 genes, and its ability to predict the risk of osteoporosis was verified in the discovery cohort. RT-qPCR verified the expression of potential biomarkers and showed a strong correlation with BMD. The functional annotation results of the DEGs showed that the diagnostic signature might affect the occurrence and development of PMOP through multiple biological pathways. In addition, 5 candidate molecules related to diagnostic signatures were screened out.Conclusion: Our diagnostic signature can effectively predict the risk of PMOP, with potential application for clinical decisions and drug candidate selection.

Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by porcine epidemic diarrhea virus (PEDV). PED causes enteric disorders with an exceptionally high fatality in neonates, bringing substantial economic losses in the pork industry. The trimeric spike (S) glycoprotein of PEDV is responsible for virus-host recognition, membrane fusion, and is the main target for vaccine development and antigenic analysis. The atomic structures of the recombinant PEDV S proteins of two different strains have been reported, but they reveal distinct N-terminal domain 0 (D0) architectures that may correspond to different functional states. The existence of the D0 is a unique feature of alphacoronavirus. Here we combined cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to demonstrate in situ the asynchronous S protein D0 motions on intact viral particles of a highly virulent PEDV Pintung 52 strain. We further determined the cryo-EM structure of the recombinant S protein derived from a porcine cell line, which revealed additional domain motions likely associated with receptor binding. By integrating mass spectrometry and cryo-EM, we delineated the complex compositions and spatial distribution of the PEDV S protein N-glycans, and demonstrated the functional role of a key N-glycan in modulating the D0 conformation.

Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. Male Sprague–Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF.

Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologically based rhythm control of AF has not proven to be superior to rate control. Ablation-based rhythm control was compared with rate control to evaluate if clinical outcomes in patients with HF and AF could be improved. Methods: This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high-burden paroxysmal (>4 episodes in 6 months) or persistent (duration Results: From December 1, 2011, to January 20, 2018, 411 patients were randomly assigned to ablation-based rhythm control (n=214) or rate control (n=197). The primary outcome occurred in 50 (23.4%) patients in the ablation-based rhythm-control group and 64 (32.5%) patients in the rate-control group (hazard ratio, 0.71 [95% CI, 0.49–1.03]; P =0.066). Left ventricular ejection fraction increased in the ablation-based group (10.1±1.2% versus 3.8±1.2%, P =0.017), 6-minute walk distance improved (44.9±9.1 m versus 27.5±9.7 m, P =0.025), and NT-proBNP demonstrated a decrease (mean change –77.1% versus –39.2%, P P =0.0036), as did the AF Effect on Quality of Life score (least-squares mean difference of 6.2 [95% CI, 1.7–10.7]; P =0.0005). Serious adverse events were observed in 50% of patients in both treatment groups. Conclusions: In patients with high-burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control versus rate control; however, there was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01420393.

Many people use smart speakers at home nowadays for various reasons, such as playing music, checking news and weather, setting timers/alarms, etc. However, before smart speakers were created and available on the market, people used to have home audio systems for similar applications. Nonetheless, the control systems of smart speakers have many different appearances. Affordance is the information given by an object, which is determined by its appearance and supplies clues about its appropriate operation. Therefore, smart speakers should have affordances. Since smart speakers are the main device in the sustainable lifestyle of human beings in smart homes, this study analyzed the affordances of its appearance affect people and the result is essential to the sustainability of smart home. The present study presents a review of the smart speakers in Taiwan, focusing on the four main affordances (physical, cognitive, sensory, functional) and three different age groups (60 participants) based on four appearance categories of smart speaker control, namely, mechanical button control, no-button–no-touch control, touchscreen control, and touch sensor control. By examining the comparison of three age groups, 18–24, 25–49 and 50+, the results of one-way ANOVA showed that the smart speakers with touchscreen control and touch sensor control had a significant difference (p < 0.01) in four main affordances among these three age groups. The smart speakers with mechanical button control and no-button–no-touch control had no significant difference (p > 0.01) in four main affordances among these three age groups. In conclusion, age-range and cultural group affect the affordance of smart home speakers.

Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD.A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients.Acr-dG levels were statistically correlated with CKD stages in UC patients (P0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P0.005).These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with the recurrence of bladder cancer. Previous studies have shown that activation of FGFR and HER2 signaling are involved in bladder cancer cell proliferation and drug resistance. Smoking is the most common etiologic risk factor for bladder cancer, and there is emerging evidence that smoking is associated with cisplatin resistance. However, the underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes. Our previous studies have shown that acrolein contributes to bladder carcinogenesis through the induction of DNA damage and inhibition of DNA repair. In this study, we found that acrolein induced cisplatin resistance and tumor progression in both non–muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) cell lines RT4 and T24, respectively. Activation of HER2 and FGFR3 signaling contributes to acrolein-induced cisplatin resistance in RT4 and T24 cells, respectively. Furthermore, trastuzumab, an anti-HER2 antibody, and PD173074, an FGFR inhibitor, reversed cisplatin resistance in RT4 and T24 cells, respectively. Using a xenograft mouse model with acrolein-induced cisplatin-resistant T24 clones, we found that cisplatin combined with PD173074 significantly reduced tumor size compared with cisplatin alone. These results indicate that differential molecular alterations behind cisplatin resistance in NMIBC and MIBC significantly alter the effectiveness of targeted therapy combined with chemotherapy. This study provides valuable insights into therapeutic strategies for cisplatin-resistant bladder cancer.

Based on the self-terminating thermal oxidation-assisted wet etching technique, two kinds of enhancement mode Al2O3/GaN MOSFETs (metal–oxide–semiconductor field-effect transistors) separately with sapphire substrate and Si substrate are prepared. It is found that the performance of sapphire substrate device is better than that of silicon substrate. Comparing these two devices, the maximum drain current of sapphire substrate device (401 mA/mm) is 1.76 times that of silicon substrate device (228 mA/mm), and the field-effect mobility (μ FEmax) of sapphire substrate device (176 cm2/V⋅s) is 1.83 times that of silicon substrate device (96 cm2/V⋅s). The conductive resistance of silicon substrate device is 21.2Ω ⋅mm, while that of sapphire substrate device is only 15.2Ω ⋅mm, which is 61% that of silicon substrate device. The significant difference in performance between sapphire substrate and Si substrate is related to the differences in interface and border trap near Al2O3/GaN interface. Experimental studies show that (i) interface/border trap density in the sapphire substrate device is one order of magnitude lower than in the Si substrate device, (ii) Both the border traps in Al2O3 dielectric near Al2O3/GaN and the interface traps in Al2O3/GaN interface have a significantly effect on device channel mobility, and (iii) the properties of gallium nitride materials on different substrates are different due to wet etching. The research results in this work provide a reference for further optimizing the performances of silicon substrate devices.

An innovative 3D printing procedure for producing a highly porous AgCl/Ag0 photocatalyst was developed and tested for its stability and degradability of azo dye (Orange II) and bacteria (Escherichia coli). The AgCl/Ag0 photocatalytic module was fabricated through selective laser melting (SLM), in which the AgCl powder was stacked in a thin layer (approximate average thickness of 30 μm) on a platform and melted by a high-power laser beam layer by layer until the 3D module was created. The melting process may cause AgCl to transform into other compounds, which may, in turn, reduce the activity of photocatalysts; for this reason, the optimal laser power and scanning speed for constructing an SLM module were investigated; they were determined to be 26 W and at 385 mm/s. This photocatalytic module effectively degraded azo dye and sterilized E. coli. The degradation of azo dye was performed under visible and UV light irradiation, and the degradation kinetics was first-order reactions. Furthermore, the azo dye degradability (95%) of this photocatalyst module persisted for five cycles in our experiment. The sterilization of E. coli was accomplished within a 135-min test, and the degradation kinetics was also first-order reactions. The photocatalytic module fabricated through SLM not only exhibited the ability to degrade contaminants in the water but also had durability and reliability after repeated use.

We have previously shown that GSH depletion alters global metabolism of cells. In the present study, we applied a metabolomic approach for studying the early changes in metabolism in hydrogen peroxide- (H2O2-) treated hepatoma cells which were destined to die. Levels of fructose 1,6-bisphosphate and an unusual metabolite, sedoheptulose 1,7-bisphosphate (S-1,7-BP), were elevated in hepatoma Hep G2 cells. Deficiency in G6PD activity significantly reduced S-1,7-BP formation, suggesting that S-1,7-BP is formed in the pentose phosphate pathway as a response to oxidative stress. Additionally, H2O2treatment significantly increased the level of nicotinamide adenine dinucleotide phosphate (NADP+) and reduced the levels of ATP and NAD+. Severe depletion of ATP and NAD+in H2O2-treated Hep G2 cells was associated with cell death. Inhibition of PARP-mediated NAD+depletion partially protected cells from death. Comparison of metabolite profiles of G6PD-deficient cells and their normal counterparts revealed that changes in GSH and GSSG per se do not cause cell death. These findings suggest that the failure of hepatoma cells to maintain energy metabolism in the midst of oxidative stress may cause cell death.

Eye drops are a conventional method of drug delivery to the eye, accounting for 90% of currently accessible ophthalmic formulations. The major problem with eye drop treatments is rapid pre-corneal drug loss. Furthermore, the need for frequent administration of eye drops can profoundly affect the quality of life of ophthalmological patients. In the current study, we developed a liposomal nanoparticle encapsulated with chloramphenicol mixed with biodegradable materials against ophthalmological disease. We first established a protocol for chloramphenicol (CAP) loaded into liposomal nanoparticle (LipoCAP). We also established the collagen/gelatin/sodium alginate (CGA) as the component of biodegradable polymers and calibrated the novel drug-releasing formulation. Finally, we combined LipoCAP with CGA to generate an 8-hour degradable ophthalmic chloramphenicol gel, CGA-LipoCAP-8. CGA-LipoCAP-8 reached the effective working concentration in 75 minutes and prolonged the drug-releasing time for at least 12 hours. In addition, CGA-LipoCAP-8 could stably and continuously inhibit E. coli proliferation. The inhibiting phenomenon was more pronounced over time. Furthermore, there were no significant toxicities observed when CGA-LipoCAP-8 co-cultured with ocular epithelial cells. In conclusion, CGA-LipoCAP-8 achieved effective CAP dose concentrations in a short time and sustained CAP release for a prolonged period. Our results provide an innovative concept in relation to novel drug-release formulations, with safety and efficiency supporting use in future treatments for ophthalmological diseases.

The association between bladder cancer mortality-to-incidence ratios (MIRs) and healthcare disparities has gender differences. However, no evidence supports gender as an issue in the association between changes in the MIR and health expenditures on bladder cancer. Changes in the MIR were defined as the difference in data from the years 2012 and 2018, which was named δMIR. Current health expenditures (CHE) and the human development index (HDI) were obtained from the World Health Organization and the Human Development Report Office. The association between variables was analyzed by Spearman’s rank correlation coefficient. In total, 55 countries were analyzed according to data quality and the exclusion of missing data. Globally, the MIR changed according to the HDI level in both genders. Among the 55 countries studied, a high HDI and CHE were significantly associated with a favorable age-standardized rate-based MIR (ASR-based MIR) in both genders and the subgroups according to gender (for both genders, MIR vs. HDI: ρ = -0.720, p < 0.001; MIR vs. CHE per capita: ρ = -0.760, p < 0.001; MIR vs. CHE as a percentage of gross domestic product (CHE/GDP): ρ = -0.663, p < 0.001). Importantly, in females only, the CHE/GDP but neither the HDI score nor the CHE per capita was significantly associated with a favorable ASR-based δMIR (ASR-based δMIR vs. CHE/GDP: ρ = 0.414, p = 0.002). In the gender subgroups, the association between the HDI and the CHE was statistically significant for females and less significant for males. In conclusion, favorable bladder ASR-based MIRs were associated with a high CHE; however, improvement of the ASR-based δMIR data was more correlated with the CHE in females. Further investigation of the gender differences via a cohort survey with detailed information of clinical-pathological characteristics, treatment strategies, and outcomes might clarify these issues and improve therapeutic and/or screening strategies for bladder cancer.

In Taiwan, the landforms are mainly dominated by mountains and hills. Thus, countless road sections of the freeways are impossible to avoid the state-of-the-practice problems such as slope cutting. In order to stabilize the freeway slope, ground anchor technique is often employed to improve the stability of cut slope. With the increasing service time of ground anchors, their performance on the freeway slopes is highly required to be assessed. There were many disasters on freeway anchored slopes in recent years, so ground anchor inspection has also received attention to a great extent. This paper introduces the concept of safety potential analysis and then utilizes the proposed model for an anchored slope. Specifically, the proposed safety potential analysis collects plain map, historical slope inspections, monitoring data, ground anchor inspections and maintenance practices, as well as further use the geographic information system to establish the proposed model. Finally, this paper provides the predicted result from safety potential analysis and suggests the dangerous area of the studied anchored slope to the government authorities for immediately response purpose.

In recent years, due to the emergence of Edge Computing architecture, the microservice computing originally located in the cloud has been extended to the edge to reduce network latency. At the same time, the data transmission bandwidth is dispersed on the edge, reducing the usage of network bandwidth, and thus shortening the response time of the service. In addition, the way which the cloud manages the edge is called cloud-edge collaboration. This is the unified management of microservice operations at the edge by the cloud. And, cloud-edge collaboration can also reduce maintenance costs. KubeEdge is an open source cloud-edge collaboration architecture by using the cloud to manage multiple edge microservices. However, if there are multiple microservices that need to be continuously deployed and updated, a more complete solution is still needed in microservice management. Hence, this study proposes an edge computing architecture that apply additional component to KubeEdge to deploy and manage containerized microservices automatically.

Introduction Targeted temperature management (TTM) was shown to have favorable outcome in patients with cardiac arrest. However, there were still limited publications about the impact of the time intervalsfromreturn of spontaneous circulation (ROSC) to the initiation of TTMin patients after cardiac arrest.The aim of this study is toinvestigate the association between the time intervalsfrom ROSC to the initiation of TTMand the favorable neurological outcomes. Methods The data used the Taiwan Network of Targeted Temperature Management for Cardiac arrest (TIMECARD) registry database. Patients with cardiac arrest received TTMwere collected from June 2018 to June 2019. Very early, early, late, very late, and delayed TTM groups were defined as the time from cardiac arrest to initiation of TTM 0 to 5 hours,5 to 8 hours, 8 to 11 hours, 11 to 14 hours, and >14 hours respectively. A totalof 559 patients were divided into5 groups: very early group (N=82), early (N=150), late (N=118), very late (N=71) and delayed group (N=138). Results The baseline character were not different among 5 groups. Favorable neurological outcomes (cerebral performance category 1 and 2) in the very early, early, late, very late and delayed groupswere 66.67%, 33.33%, 50%, 25%, and 14.29% respectively. The Cox analysis showed very late and delayed group had worse neurologic outcome (HR=1.829, 95% CI=1.04- 3.23, p=0.0371). There is also trend to have worse neurologic outcome in late group (HR=1.734, 95% CI=0.91- 3.30, p=0.0939). Conclusion This national registry study demonstrated that early initiation of TTM in patients with cardiac arrest was associated with improved favorable neurological outcomes compared with those with late initiation of TTM. Funding Acknowledgement Type of funding source: None

Metabolic alterations have been documented in peripheral tissues in heart failure (HF). Outcomes might be improved by early identification of risk. However, the prognostic information offered is still far from enough. We hypothesized that plasma metabolic profiling potentially provides risk stratification for HF patients. Of 61 patients hospitalized due to acute decompensated HF, 31 developed HF-related events in one year after discharge (Event group), and the other 30 patients did not (Non-event group). The plasma collected during hospital admission was analyzed by an ultra-high performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS)-based metabolomic approach. The orthogonal projection to latent structure discriminant analysis (OPLS-DA) reveals that the metabolomics profile is able to distinguish between events in HF. Levels of 19 metabolites including acylcarnitines, lysophospholipids, dimethylxanthine, dimethyluric acid, tryptophan, phenylacetylglutamine, and hypoxanthine are significantly different between patients with and without event (p &lt, 0.05). Established risk prediction models of event patients by using receiver operating characteristics analysis reveal that the combination of tetradecenoylcarnitine, dimethylxanthine, phenylacetylglutamine, and hypoxanthine has better discrimination than B-type natriuretic peptide (BNP) (AUC 0.871 and 0.602, respectively). These findings suggest that metabolomics-derived metabolic profiling have the potential of identifying patients with high risk of HF-related events and provide insights related to HF outcome.

INTRODUCTION AND OBJECTIVE:Acrolein, produced by polyamines, has been reported to be associated with bladder cancer and the level of acrolein was well correlated with chronic kidney disease (CKD). ...

The biomarkers of Parkinson’s disease (PD) remain to be investigated. This work aimed to identify blood biomarkers for PD using targeted metabolomics analysis. We quantified the plasma levels of 255 metabolites in 92 PD patients and 60 healthy controls (HC). PD patients were sub-grouped into early (Hoehn–Yahr stage ≤ 2, n = 72) and advanced (Hoehn–Yahr stage > 2, n = 20) stages. Fifty-nine phospholipids, 3 fatty acids, 3 amino acids, and 7 biogenic amines, demonstrated significant alterations in PD patients. Six of them, dihydro sphingomyelin (SM) 24:0, 22:0, 20:0, phosphatidylethanolamine-plasmalogen (PEp) 38:6, and phosphatidylcholine 38:5 and 36:6, demonstrated lowest levels in PD patients in the advanced stage, followed by those in the early stage and HC. By contrast, the level of ornithine was highest in PD patients at the advanced stage, followed by those at the early stage and HC. These biomarker candidates demonstrated significant correlations with scores of motor disability, cognitive dysfunction, depression, and quality of daily life. The support vector machine algorithm using α-synuclein, dihydro SM 24:0, and PEp 38:6 demonstrated good ability to separate PD from HC (AUC: 0.820). This metabolomic analysis demonstrates new plasma biomarker candidates for PD and supports their role in participating PD pathogenesis and monitoring disease progression.

To identify the association between metabolites and muscle mass in 305 elderly Taiwanese subjects, we conducted a multivariate analysis of 153 plasma samples. Based on appendicular skeletal muscle mass index (ASMI) quartiles, female and male participants were divided into four groups. Quartile 4 (Men: 5.67±0.35, Women: 4.70±0.32 Kg/m2) and quartile 1 (Men: 7.60±0.29, Women: 6.56±0.53 Kg/m2) represented low muscle mass and control groups, respectively. After multivariable adjustment, except for physical function, we found that blood urea nitrogen, creatinine, and age were associated with ASMI in men. However, only triglyceride level was related to ASMI in women. The multiple logistic regression models were used to analyze in each baseline characteristic and metabolite concentration. After the adjustment, we identify amino acid-related metabolites and show that glutamate levels in women and alpha-aminoadipate, Dopa, and citrulline/ornithine levels in men are gender-specific metabolic signatures of muscle mass loss.

This study aimed to measure the basal energy expenditure (BEE) of Chinese healthy adults and establish an accurate predictive equation for this population.In total, 470 Chinese healthy adults had their BEE measured using the Cosmed K4bThere was a significant difference in BEE between males and females, with 5,954 kJ/d and 5,089 kJ/d, respectively. People living in rural areas expended significantly higher BEE (5,885 kJ/d) than those in urban areas (5,279 kJ/d). Previous equations developed by Henry, Schofield, Harris-Benedict (H-B), and Liu overestimated the BEE of Chinese healthy adults. The new equations derived from the present study displayed the smallest average bias and RMSE from the measured basal energy expenditure (mBEE). The CCC of the new equations was higher than other predictive equations, but it was lower than 0.8. There was no significant difference in the accuracy rate among all predictive equations.Sex and regional differences in BEE were observed in Chinese healthy adults. Neither the widely used previous predictive equations nor the one derived in the present study were accurate enough for estimating the BEE of Chinese healthy adults. Further study is required to develop more accurate equations for predicting the BEE of Chinese healthy adults aged between 20-45 years.

A pruned Volterra equalizer that reduces computational complexity by up to 85.2% in 112-Gbps PAM-4 optical interconnects is proposed. The BER performance is competitive with LASSO-based Volterra equalizers, and training time is twice as fast.

Aging is a complex progression of biological processes and is the causal contributor to the development of diabetes mellitus (DM). DM is the most common degenerative disease and is the fifth leading cause of death in Taiwan, where the trend of DM mortality has been steadily increasing. Metabolomics, important branch of systems biology, has been mainly utilized to understand endogenous metabolites in biological systems and their dynamic changes as they relate to endogenous and exogenous factors. The purpose of this study was to elucidate the metabolomic profiles in elderly people and its relation to lipid disorder (LD). We collected 486 elderly individuals aged &ge, 65 years and performed untargeted and targeted metabolite analysis using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography&mdash, mass spectrometry (LC/MS). Several metabolites, including branched-chain amino acids, alanine, glutamate and alpha-aminoadipic acid were elevated in LD compared to the control group. Based on multivariate analysis, four metabolites were selected in the best model to predict DM progression: phosphatidylcholine acyl-alkyl (PC ae) C34:3, PC ae C44:3, SM C24:1 and PCae C36:3. The combined area under the curve (AUC) of those metabolites (0.82) was better for DM classification than individual values. This study found that targeted metabolic signatures not only distinguish the LD within the control group but also differentiated DM from LD in elderly Taiwanese. These metabolites could indicate the nutritional status and act as potential metabolic biomarkers for the elderly in Taiwan.

The mortality-to-incidence ratio (MIR) is associated with the clinical outcome of cancer treatment. For several cancers, countries with relatively good health care systems have favorable MIRs. However, the association between lung cancer MIR and health care expenditures or rankings has not been evaluated. We used linear regression to analyze the correlation between lung cancer MIRs and the total expenditures on health/gross domestic product (e/GDP) and the World Health Organization (WHO) rankings. We included 57 countries, for which data of adequate quality were available, and we found high rates of incidence and mortality but low MIRs in more developed regions. Among the continents, North America had the highest rates of incidence and mortality, whereas the highest MIRs were in Africa, Asia, Latin America, and the Caribbean. Globally, favorable MIRs correlated with high e/GDP and good WHO ranking (regression coefficient, &minus, 0.014 and 0.001, p = 0.004, and p = 0.014, respectively). In conclusion, the MIR for lung cancer in different countries varies with the expenditure on health care and health system rankings.

Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to NASH is not understood. Lipid overload causing lipotoxicity and inflammation has been considered as an essential pathogenic factor. To correlate the lipid profiles with cellular lipotoxicity, we utilized palmitic acid (C16:0)- and especially unprecedented palmitoleic acid (C16:1)-induced lipid overload HepG2 cell models coupled with lipidomic technology involving labeling with stable isotopes. C16:0 induced inflammation and cell death, whereas C16:1 induced significant lipid droplet accumulation. Moreover, inhibition of de novo sphingolipid synthesis by myriocin (Myr) aggravated C16:0 induced lipoapoptosis. Lipid profiles are different in C16:0 and C16:1-treated cells. Stable isotope-labeled lipidomics elucidates the roles of specific fatty acids that affect lipid metabolism and cause lipotoxicity or lipid droplet formation. It indicates that not only saturation or monounsaturation of fatty acids plays a role in hepatic lipotoxicity but also Myr inhibition exasperates lipoapoptosis through ceramide in-direct pathway. Using the techniques presented in this study, we can potentially investigate the mechanism of lipid metabolism and the heterogeneous development of NAFLD.

This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus.The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers. After 37 days, the zinc concentrations in the plasma and hippocampus were measured, and the behavioral function of the offspring rats was measured using the passive avoidance performance test. We then assessed the DNA methylation patterns of the exon IX of BDNF by methylation-specific quantitative real-time PCR and the mRNA expression of BDNF in the hippocampus by RT-PCR.Compared with the ZA and PF groups, rats in the ZD group had shorter latency period, lower zinc concentrations in the plasma and hippocampus (P 0.05). Interestingly, the DNA methylation of the BDNF exon IX was significantly increased in the ZD group, compared with the ZA and PF groups, whereas the expression of the BDNF mRNA was decreased. In addition, the DNMT1 mRNA expression was significantly upregulated and DNMT3A was downregulated in the ZD group, but not in the ZA and PF groups.The learning and memory damage in offspring may be a result of the epigenetic changes of the BDNF genes in response to the zinc-deficient diet during 0∼2 month period. Furthermore, this work supports the speculative notion that altered DNA methylation of BDNF in the hippocampus is one of the main causes of cognitive impairment by zinc deficiency.

The mortality-to-incidence ratio (MIR) is associated with the clinical outcomes of different types of cancer as well as the ranking of health care systems. However, the association between MIRs for testicular cancer and health care disparities, including differences in expenditures and health system rankings, has not yet been reported. We used the Spearman&rsquo, s rank correlation coefficient (CC) to analyze the correlation between testicular cancer MIRs and both total expenditures on health/gross domestic product (e/GDP) and the World Health Organization&rsquo, s (WHO) health system rankings. After screening the data for quality and missing information, 57 countries were chosen for analysis. Generally, developed countries and regions had relatively high rates of incidence/mortality, but with a favorable MIR. Among the continents, Europe had the highest incidence rates, whereas the highest MIRs were in Africa. Globally, favorable testicular cancer MIRs were observed in countries with both a high e/GDP and a good WHO ranking (R2 = 0.325, p &lt, 0.001 and CC = &minus, 0.568, p &lt, 0.001, R2 = 0.367, p &lt, 0.001 and CC = 0.655, p &lt, 0.001, respectively). In conclusion, the MIR for testicular cancer varies in countries and regions based on both their total health expenditure and their health care system ranking.

Background The advancements in cancer therapy have improved the clinical outcomes of cancer patients in recent decades. However, advanced cancer therapy is expensive and requires good health care systems. For kidney cancer, no studies have yet established an association between clinical outcome and health care disparities. Methods We used the mortality-to-incidence ratio (MIR) for kidney cancer as a marker of clinical outcome to compare World Health Organization (WHO) country rankings and total expenditures on health/gross domestic product (e/GDP) using linear regression analyses. Results We included 57 countries based on data from the GLOBOCAN 2012 database. We found that more highly developed regions have higher crude and age-standardized rates of kidney cancer incidence and mortality, but a lower MIR, when compared to less developed regions. North America has the highest crude rates of incidence, but the lowest MIRs, whereas Africa has the highest MIRs. Furthermore, favorable MIRs are correlated with countries with good WHO rankings and high e/GDP expenditures (p

Background Identification of novel biomarkers is needed to improve the diagnosis and prognosis of heart failure (HF). Metabolic disturbance is remarkable in patients with HF. Objectives This study sought to assess the diagnostic and prognostic values of metabolomics in HF. Methods Mass spectrometry–based profiling of plasma metabolites was performed in 515 participants; the discovery phase study enrolled 51 normal control subjects and 183 HF patients, and the validation study enrolled 63 control subjects and 218 patients with stage C HF. Another independent group of 32 patients with stage C HF who recovered to New York Heart Association functional class I at 6 and 12 months was profiled as the “recovery” group. Results A panel of metabolites, including histidine, phenylalanine, spermidine, and phosphatidylcholine C34:4, has a diagnostic value similar to B-type natriuretic peptide (BNP). In the recovery group, the values of this panel significantly improved at 6 and 12 months. To evaluate the prognostic values, events were defined as the combined endpoints of death or HF-related re-hospitalization. A metabolite panel, which consisted of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine, and the total amount of essential amino acids, provided significant prognostic values (p Conclusions Metabolomics demonstrate powerful diagnostic value in estimating HF-related metabolic disturbance. The profile of metabolites provides better prognostic value versus conventional biomarkers.

A dual-functional sensor based on silver nanoparticles was synthesized by a two-stage procedure consisting of a low-temperature chitosan-Ag(+) complexation followed by a high-temperature reduction of the complex to form chitosan-capped silver nanoparticles (CS-capped Ag NPs). The surface plasmon resonance (SPR) absorption and fluorescence emission of the silver nanoparticles were influenced by the concentration and degradation time of chitosan, and the temperatures of the complexation and reduction reactions. The SPR absorption band was blue-shifted while the intensities of emission and absorption were decreased after reacting the silver nanoparticles with Hg(2+) ions. The silver nanoparticles reacted with Hg(2+) were characterized by high resolution transmission electron microscopy (HRTEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and surface-enhanced Raman scattering spectroscopy (SERS). The results suggested that the particle growth and aggregation of the silver nanoparticles were caused by the adsorption of Hg(2+) and deposition of Hg(0) on the nanoparticle surface. Direct correlations of the SPR absorption and fluorescence emission with the concentration of Hg(2+) were useful for quantitative analysis of Hg(2+). It was possible to use the dual-functional silver nanoparticles as a colorimetric and fluorescent sensor for sensitive and selective detection of Hg(2+) ions.

Objective To enhance the quality of medical service for Chinese patients through research of service quality from Chinese medical personnel. Methods ServQual scale was used for infection medical staffs randomly by sampling questionnaire in Beijing, Shanghai, Chengdu, Chongqing, Guangzhou and Nanning. The data collected were entered and analyzed using SPSS 20.0. Statistical methods included frequency, factor analysis, reliability analysis, correlation analysis, independent samples t test, one-way analyses of variance, simultaneous regression analysis and structural equation model analysis. Results The Kaiser-Meyer-Olkin value for the factor analysis of the scale was 0.970. The Cronbach’s α for the reliability analysis was 0.975. The Pearson correlation coefficients were 0.624-0.874 and statistically significant. Undergraduates felt good, PhD students felt bad; the doctors felt bad; managers felt good. Standard 5 dimensions of the regression coefficients were positive, including empathy (β = 0.288), reliability (β = 0.241) impacting on perceived service quality mostly. The control ability and stability of the standard error of perceived service quality directly effected value were 0.646 and 0.382, respectively. Conclusions Medical staffs of infectious disease department have poor perception of service quality. Hospitals should improve awareness and of clinicians and deepen the reform of the medical care system.

Lipids play an important role in the pathogenesis of cardiovascular disease. Changes in lipids of erythrocytes are indicative of the outcome of pathophysiological processes. In the present study, we assessed whether the lipid profiles of erythrocytes from heart failure (HF) patients are informative of their disease risk. The lipidomes of erythrocytes from 10 control subjects and 29 patients at different HF stages were analyzed using liquid chromatography time-of-flight mass spectrometry. The lipid composition of erythrocytes obtained from HF patients was significantly different from that of normal controls. The levels of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and sphingomyelins decreased in HF erythrocytes as compared with those of control subjects; however, the levels of lysoPCs, lysoPEs, and ceramides increased in HF erythrocytes. Notably, the oxidized cholesterol 7-ketocholesterol (7KCh) accumulated to higher level in HF erythrocytes than in plasma from the same patients. We further validated our findings with a cohort of 115 subjects of control subjects (n=28) and patients (n=87). Mechanistically, 7KCh promoted reactive oxygen species (ROS) formation in cardiomyocytes; and induced their death, probably through an ATF4-dependent pathway. Our findings suggest that erythrocytic 7KCh can be a risk factor for HF, and is probably implicated in its pathophysiology. Keywords: Heart failure, Lipidomics, 7-ketocholesterol, Oxidative stress

Guillain-Barre Syndrome (GBS) is an inflammatory disease of the peripheral nervous system. Given that plasma metabolic profiles in GBS patients have never been explored, plasma samples of 38 GBS patients, 22 multiple sclerosis (MS) patients, and 40 healthy controls were analyzed by using untargeted and targeted metabolomics analysis. The untargeted analysis showed that levels of a set of plasma lipid metabolites were significantly decreased in GBS patients compared to the controls. Furthermore, the targeted analysis demonstrated that levels of 41 metabolites in GBS patients were significantly changed compared to either the controls or MS patients. A further metabolic analysis showed that 12 of 41 metabolites were significantly lower in classical GBS patients compared to Miller-Fisher syndrome. Among them, each of PCae C34:0, PCae C42:2, PCae C42:3, and SM C24:0 was inversely correlated with Hughes functional grading scale of GBS patients at both nadir and discharge. Receiver operating characteristic curve analysis of combination of three metabolites (PCaa C42:2, PCae C36:0 and SM C24:0) showed a good discrimination between the GBS and the controls (area under curve = 0.86). This study has demonstrated disruption of lipid metabolites in GBS may be potential biomarkers to indicate disease severity and prognosis of GBS.

Background Guillain-Barre syndrome (GBS) is an acute inflammatory polyneuropathy resulting in demyelination in peripheral nervous system. Myelin enriched in lipids is easily oxidized by reactive oxygen species during inflammation. Oxidative stress and lipophilic anti-oxidative capacities in GBS patients have not been fully explored. To evaluate the redox status of GBS patients, we measured malondialdehyde (MDA), myeloperoxidase (MPO), lipophilic antioxidants, and tocopherols concentrations in plasma from GBS patients and age-matched healthy controls. Results Concentrations of γ-tocopherol and δ-tocopherol decreased significantly, and α-carotene significantly increased in GBS patients compared to healthy controls. However, no significant changes in MDA and MPO concentrations were detected. In GBS patients, the γ-tocopherol concentration correlated positively with concentrations of δ-tocopherol, α-tocopherol, lutein, Q10, and γ-CEHC, respectively. Similarly, the δ-tocopherol concentration correlated positively with γ-tocopherol, α-tocopherol, lutein, Q10, δ-CEHC, and γ-CEHC concentrations, respectively. The receiver operating characteristics curve analysis showed that γ-tocopherol may serve as a good predictor for GBS. Conclusions Diminished lipophilic antioxidant defense, mainly γ-tocopherol and δ-tocopherol, in GBS patients accounting for their lowered resistance to reactive oxygen species is probably associated with pathogenesis of GBS, and potentially useful for the development of therapeutic strategies.

This paper presents a bi-orthogonal waveform optimization for frequency division multiplexing signaling to support massive connections feature in Internet-of-Things (IoT). Increasing the number of subcarriers within a narrow bandwidth helps to support massive connections in the system. In this paper, we try to optimize the bi-orthogonal pulse shaping to reduce inter-symbol interference (ISI) and inter-carrier interference (ICI) for Bi-orthogonal Frequency Division Multiplexing (BFDM) in a mobile environment. We apply B-splines and Gaussian pulses with the canonical Gabor tight window to calculate receive pulses. In particular, the pulse in BFDM is optimized by minimizing the tail of the ambiguity function to reduce ISI and ICI. The numerical simulation is provided to evaluate the signal-to-interference ratio (SIR) and the number of supporting subcarriers in doubly dispersive channels. The simulation shows that the bi-orthogonal pulse shape optimization in BFDM helps to reduce the ISI/ICI so that the number of supporting subcarriers within a fixed bandwidth can be increased by around two orders of magnitude.

In this study, JIS SUS202 stainless steel wires are rapidly welded by induction heating using a current at a frequency of 2 MHz. The effects of the heating parameters on the mechanical properties and microstructures of the joint are investigated. After induction welding, the main structures in the joint of the 202 stainless steel wires are austenite and ferrite. The amount of ferrite increases by increasing the heating temperature or heating time. Moreover, the tensile strength of the joint is superior for a higher welding temperature.

A bacterial β-galactosidase delivery system is a potential therapy for lactose intolerance. Currently, two Lactobacillus bulgaricus strains with different biological characteristics are under consideration as potential sources. However, differences in these β-galactosidase genes and their resulting production levels are poorly characterized. The β-galactosidase ORF of L. bulgaricus yogurt isolate had high variability and was terminated at site 1924 due to a stop codon. However, the full 114 kDa β-galactosidase band was still resolved by SDS-PAGE, which may indicate that the interrupted ORF was translated into more than one peptide, and they together were folded into the complete enzyme protein that showed much higher β-galactosidase activity (6.2 U/mg protein) than the enzyme generated from L. bulgaricus reference strain (2.5 U/mg protein).

In order to improve the precision of gas emission forecasting,this paper proposes a new forecasting model based on Particle Swarm Optimization (PSO).PSO is a novel random optimization method which has extensive capability of global optimization.In the model, PSO is used to optimize the weight,width and center of RBF neural network and the optimal model is applied to forecast gas emission.The diversified factors analysised with grey correlation,MATLAB is employed to implement the model for gas emission forecasting.The simulation results show that the gas emission model optimized by PSO is more accurate than the traditional RBF model．

In this study, nanoparticle (NP, diameter 100 nm during bagging or feeding processes, unless there were combustion-related incidental sources existed. Large fraction of nanomaterials was found in the RPM due to agglomeration of nanomaterials or attachment of nanomaterials to the larger particles. From this study, it is concluded that RPM concentration measurements are necessary for the exposure assessment of nanoparticles in workplaces.

A humidity control system was operated upstream of two collocated MOUDIs (micro-orifice uniform deposit impactors) for sampling ambient aerosol particles. One MOUDI used silicone-grease-coated aluminum foils (ALs) as the impaction substrates and was considered as the reference impactor, while the other used uncoated ALs or uncoated Teflon filters (TFs) as the impaction substrates for quantifying the effect of different relative humidities (RHs) and impaction substrates on the PM0.1 concentrations and mass distributions of ambient PMs. Test results showed that decreasing RH in general increased particle bounce from uncoated substrates with the bounce from uncoated ALs being more severe than that from uncoated TFs. Particle bounce did not influence the overall mass distribution of ambient fine particles when RH ranged between 40% and 80%, whereas it led to undersampling of particles greater than 2.5 μm in aerodynamic diameter severely. Oversampling of PM0.1 occurred by as much as 95%–180% or 25%–55% when th...

Recombinant Lactococcus lactis MG1363/pMG36e-lacZ exhibiting high β-galactosidase activities were constructed by us in the previous study. However, erythromycin resistance present in these recombinants restricted their practical application in food preparation. This study was conducted to delete the gene coding for erythromycin resistance present in recombinant L. lactis, as a result of which these bacteria express food-grade β-galactosidase. In this study, the recombinant plasmid pMG36e-lacZ was digested with restriction enzymes BclI and HpaI and the food-grade plasmid FGZW was rebuilt. FGZW was transformed into Escherichia coli JM109 and L. lactis MG1363. Erythromycin resistance, enzyme activity determination, gene sequencing and SDS-PAGE analysis indicated that these new recombinant bacteria lost erythromycin resistance and its relevant gene but still expressed β-galactosidase activities, although a decrease in the expression of β-galactosidase of these new strains was observed. The β-galactosidase food-grade expression system was successfully constructed and it could provide a new solution for the management of lactose intolerance. These results might promote the usage of gene-modified microorganisms and related technology in the food sector, which has the highest priority for food safety.