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In this study, in situ electrochemical synthesis of Ni–Mg–Al–LDHs for the treatment of simulated strontium-containing liquid radioactive waste (LRW) from nuclear power plants. The optimal reaction conditions were obtained by single-factor experiments: initial pH of 12, Mg electrode current density (JMg) of 12.5 mA/cm2, Ni–Mg–Al metal molar ratio (RNi_Mg–Al) of 3:1:1 and reaction temperature (T) of 30 °C. The removal rate of Sr2+ can reach up to 99.65%. The synthetic precipitate was characterized by XRD, FESEM-EDS and FT-IR under optimal reaction conditions. The XRD pattern showed that the main component of the precipitate is Ni–Mg–Al–LDHs. The precipitate was characterized by FESEM to have distinct layered double hydroxides (LDHs) structure. The absorption peaks of O–H bonds, C–O bonds, and M–O–M (M is Ni, Mg and Al) bonds appeared in IR spectrum. The method of in situ electrochemical synthesis of Ni–Mg–Al–LDHs has promising applications in the treatment of LRW. [ABSTRACT FROM AUTHOR]

In this study, in-situ electrochemical synthesis of monohydric phosphate intercalated layered double hydroxides (LDHs) was used to remove Sr2+ from the simulated liquid radioactive wastes. The optimum reaction conditions were obtained by response surface methodology (RSM). The removal of Sr2+ can reach up to 99.30% and the adsorption capacity of Zn–Al–LDHs–HPO4 toward Sr2+ was 6.01 mg/g under optimal conditions. With Sr2+ being removed mainly by multilayer chemisorption, the adsorption kinetics followed Lagergren pseudo-second-order kinetic model, and the adsorption isotherms followed Freundlich model. Thermodynamic studies of adsorption showed that the adsorption of Sr2+ to LDHs was a spontaneous and endothermic process. This method of LDHs synthesis simplifies the operational steps and is a promising treatment method because of its low energy consumption, high efficiency and small solid waste volume. This study provides an innovative idea for the treatment of strontium-containing liquid radioactive wastes from nuclear power plants. [ABSTRACT FROM AUTHOR]

Crack initiation, propagation, and coalescence are important for the understanding of rock mass behavior. In this paper, we use an improved numerical manifold method (NMM) that can stimulate the initiation, propagation, and coalescence of many cracks simultaneously to model the continuous–discontinuous deformation of granite under uniaxial and confined compression. This new simulation method couples subcritical crack growth (SCG) theory and the Mohr–Coulomb strength criterion with tension cut-off to consider the propagation of virtual and real cracks, respectively, and uses a statistical Weibull distribution to study the influence of elastic modulus inhomogeneity on crack propagation and rock failure. The mechanical behavior and failure modes of the models are in good agreement with experimental data. Increasing elastic modulus inhomogeneity decreases strength and the strain required for macroscopic failure. The stress corrosion index (n) and crack growth constant (C) also have a strong influence on uniaxial compressive strength. Indeed, higher values of C and n result in faster virtual crack speeds, a lower uniaxial compressive strength, and a lower axial strain upon failure. Confining pressure also exerts an influence on crack propagation, compressive strength, and failure mode. Our study shows that the improved NMM code combined with the virtual crack model is therefore an effective and reliable method to simulate crack initiation, propagation, and coalescence in granite under uniaxial and confined compression. Highlights: A virtual crack approach combined with subcritical crack growth theory is implemented in numerical manifold method to simulate the initiation of multi-cracks. The Mohr–Coulomb criterion with tension cut-off coupled with subcritical crack growth theory is incorporated into numerical manifold method to simulate the propagation of micro-and macro-cracks. Three types of crack intersection are identified in numerical manifold method to allow the model to accurately simulate the propagation and coalescence of multi-cracks and large displacement. [ABSTRACT FROM AUTHOR]

We study multistage distributionally robust mixed-integer programs under endogenous uncertainty, where the probability distribution of stage-wise uncertainty depends on the decisions made in previous stages. We first consider two ambiguity sets defined by decision-dependent bounds on the first and second moments of uncertain parameters and by mean and covariance matrix that exactly match decision-dependent empirical ones, respectively. For both sets, we show that the subproblem in each stage can be recast as a mixed-integer linear program (MILP). Moreover, we extend the general moment-based ambiguity set in Delage and Ye (Oper Res 58(3):595–612, 2010) to the multistage decision-dependent setting, and derive mixed-integer semidefinite programming (MISDP) reformulations of stage-wise subproblems. We develop methods for attaining lower and upper bounds of the optimal objective value of the multistage MISDPs, and approximate them using a series of MILPs. We deploy the Stochastic Dual Dynamic integer Programming (SDDiP) method for solving the problem under the three ambiguity sets with risk-neutral or risk-averse objective functions, and conduct numerical studies on multistage facility-location instances having diverse sizes under different parameter and uncertainty settings. Our results show that the SDDiP quickly finds optimal solutions for moderate-sized instances under the first two ambiguity sets, and also finds good approximate bounds for the multistage MISDPs derived under the third ambiguity set. We also demonstrate the efficacy of incorporating decision-dependent distributional ambiguity in multistage decision-making processes. [ABSTRACT FROM AUTHOR]

Based on the perturbative quantum chromodynamics (pQCD) approach and the quasi-two-body approximation, we have studied the three-body decays B s 0 → ψ (3686 , 3770) K π , which include the contributions of the intermediate resonances K ¯ 0 ∗ (1430) 0 , K ¯ ∗ (892) 0 , K ¯ ∗ (1410) 0 , K ¯ ∗ (1680) 0 , and K ¯ 2 ∗ (1430) 0 . The time-like form factors corresponding to the distribution amplitudes of the S-, P-, and D-wave of the kaon–pion pair were adopted in parameterized form, and describe the interactions between K and π in the resonance region. First, the decays B s 0 → ψ (2 S , 1 D) K - π + were calculated, followed by the calculation of the branching ratios of the decays B s 0 → ψ (3686 , 3770) K - π + using the 2S–1D mixing scheme. In addition, the pQCD predictions for the decays B s 0 → ψ (2 S , 1 D) K π and B s 0 → ψ (3686 , 3770) K π were obtained using the narrow-width approximation relation given by the Clebsch–Gordan coefficients. Our work shows that the K ¯ ∗ (892) 0 resonance is the main contributor to the total decay, and the branching ratio and the longitudinal polarization fraction of the ψ (2 S) K ¯ ∗ (892) 0 decay mode agree well with the currently available data within errors. Furthermore, the theoretical predictions of the ψ (2 S) and ψ (3686) decay modes are very close, indicating that they can be regarded as the same meson state. Finally, the pQCD predictions for branching ratios of decays B s 0 → ψ (3686 , 3770) K π are of the order of 10 - 5 and 10 - 6 , respectively, which can be verified using the ongoing LHCb and Belle II experiments. [ABSTRACT FROM AUTHOR]

Purpose: To assess the accuracy of gadobenate-enhanced MRI for predicting microvascular invasion (MVI) in patients operated for hepatocellular carcinoma (HCC). Methods: The 164 patients who met the inclusion criteria were assigned to one of two groups: the MVI-positive group and the MVI-negative group. Imaging results were compared between the two groups using the Kruskal test, chi-square test, independent sample t test, and logistic regression analysis. Results: Differences in the capsule (p = 0.037) and margin (p = 0.004) of the tumor, rim enhancement (p = 0.002), peritumoral enhancement in the arterial phase (p < 0.001), and peritumoral hypointensity in the hepatobiliary phase (HBP) (p < 0.001) were statistically significant. The results of multivariate analysis identified rim enhancement in the arterial phase (odds ratio (OR) = 2.115; 95% confidence interval (CI), 1.002–4.464; p = 0.049) and peritumoral hypointensity in the HBP (OR = 5.836; 95% CI, 2.442–13.948; p < 0.001) as independent risk factors for MVI. Use of the two predictors in combination identified 32.79% (20/61) of HCCs with MVI with a specificity of 95.15% (98/103). Conclusions: Rim enhancement in the arterial phase and peritumoral hypointensity in the HBP were identified as independent risk factors for MVI in patients with HCC. Key Points: • Rim enhancement in the arterial phase and peritumoral hypointensity in the hepatobiliary phase were independent risk factors for microvascular invasion in patients with HCC. • Use of the two predictors in combination had a sensitivity of 32.79% and a specificity of 95.15% for predicting microvascular invasion. [ABSTRACT FROM AUTHOR]

Objectives: To determine the sensitivity and positive predictive value (PPV) of gadobenate-enhanced MR imaging for the detection of liver metastases.Methods: This systematic review and meta-analysis was conducted according to PRISMA guidelines. A comprehensive search (EMBASE, PubMed) was performed to identify relevant articles up to December 2017. Studies eligible for inclusion were performed using appropriate methodology with complete verification by means of histopathology, intraoperative observation and/or follow-up, and sufficient information to permit determination of true-positive (TP), false-negative (FN), and false-positive (FP) values. Sources of bias were assessed using the QUADAS-2 tool. An inverse variance-weighted random-effects model was used to obtain sensitivity and PPV estimates. Information was analyzed and presented using Cochran's Q statistic, funnel plots, and modified Deeks' analysis.Results: Ten articles (256 patients, 562 metastases) were included. Sensitivity estimates for pre-contrast (unenhanced) imaging, gadobenate-enhanced dynamic imaging, and combined unenhanced, dynamic, and delayed hepatobiliary phase imaging for detecting liver metastases on a per-lesion basis were 77.8% (95% CI 71.4-84.3%, 7 assessments), 88.1% (95% CI, 84.0-92.2%, 13 assessments), and 95.1% (95% CI 93.1-97.1%, 15 assessments), respectively. The addition of hepatobiliary phase images significantly improved the detection of liver metastases. The overall PPV was 90.9% (95% CI 86.6-95.1%, 11 assessments). Deeks' funnel analysis revealed no association between sample size and sensitivity (β = 0.02, p = 0.814) indicating no significant publication bias.Conclusions: Gadobenate-enhanced MR imaging has high sensitivity and PPV for the detection of liver metastases on a per-lesion basis. The sensitivity and PPV for detection is comparable to reported values for the pure liver-specific agent gadoxetate.Key Points: • Gadobenate dimeglumine is a hepatobiliary MR contrast agent that permits acquisition of contrast-enhanced liver images during the immediate post-injection dynamic phase, like any extracellular agent, and in the delayed hepatobiliary phase, after specific uptake by the hepatocytes. • The hepatobiliary phase improves detection of liver metastases when compared either to pre-contrast unenhanced images alone or to pre-contrast + gadobenate-enhanced dynamic phase images. • The meta-analysis showed an overall sensitivity of 95.1% and PPV of 90.9% of gadobenate-enhanced MRI for the detection of metastases, when based on the evaluation of all available acquisitions. [ABSTRACT FROM AUTHOR]

The authors report on the synthesis of boron-doped carbon nanodots (B-C-dots) by a hydrothermal method using ascorbic acid and boric acid as the precursors. The dots have an irregular shape with a typical diameter of 10 nm and display strong fluorescence, with excitation/emission maxima of 350/440 nm. Fluorescence is quenched by Cu(II) and Pb(II) ions due to the formation of nonfluorescent metal complexes between chelating oxygen atoms on the surface of the dots. The findings were used to design a fluorometric method for the determination of the two ions. Linear relationships exist between the drop in fluorescence intensity and the concentrations of Cu(II) and Pb(II) ions in the range from 50 nM to 300 μM and from 25 nM to 250 μM, respectively. The fluorescence of the Cu(II)-quenched B-C-dots is restored in addition of pyrophosphate (PPi) as a result of coordination/chelation interactions between these ions and PPi. This was exploited to develop an assay for PPi that works in the of 25 to 500 μM PPi concentration range. [ABSTRACT FROM AUTHOR]

Background & Aims: Among etiologies for hepatocellular (HCC), nonalcoholic fatty liver disease (NAFLD) carries a high risk of competing non-cancer mortality. The effect of cancer and non-cancer factors on risk of death after NAFLD-HCC diagnosis remains unclear. We aimed to evaluate the role of non-cancer mortality with NAFLD-HCC. Methods: Using a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration, we identified patients with incident HCC diagnosed between January 1, 2005 and June 30, 2018. We determined cause of death as HCC-related, non-HCC liver-related, and non-liver-related after HCC diagnosis. We used Cox proportional hazards regression models to evaluate the effect of clinical factors on cause-specific mortality after NAFLD-HCC diagnosis. Results: We identified 776 patients with incident HCC. Mean age at HCC diagnosis was 70.1 year, 22.2% had Barcelona Clinic Liver Cancer (BCLC) stage 0-A, and 67.0% had more than one comorbidity. 1- and 3-year mortality rates were 47.0% and 69.6%, respectively. Most deaths (72.2% at 3 years) were attributable to HCC. In HCC patients who received curative treatment, non-cancer mortality accounted for 40% of all deaths between 3 and 5 years after treatment. Poor performance status (ECOG 3/4, HR 5.03, 95% CI: 2.59–9.77) and older age (65–75, HR 1.94, 95% CI: 1.06–3.54) were strongly associated with non-cancer mortality. Conclusion: Although most patients with NAFLD-HCC die of HCC, non-cancer mortality represents a clinically meaningful competing event for patients receiving curative treatment, underscoring the importance of assessing and managing risk factors of non-cancer morbidity and mortality. Trial and Registration: N/A. [ABSTRACT FROM AUTHOR]

We present some new characterizations on the weaving of frames and woven frames under operators, which extend and improve the corresponding works of Bemrose et al. We also provide several new ways to the construction of woven frames and, especially, we improve one known result obtained by Arabyani Neyshaburi and Arefijamaal. [ABSTRACT FROM AUTHOR]

Woodceramics is made from bamboo powder and epoxy resin. Analysis with X-ray diffraction (XRD) shows that with an increase in sintering temperature, the degree of graphitization increases. Scanning electron microscopic (SEM) analysis also indicates that bamboo powder exists in the composite as natural plant template. The study suggests that both sintering temperature and epoxy resin content have significant effects on its basic properties. Compressive strengths of woodceramics increase as sintering temperature rises but decrease as temperature rises to 1,000°C, and Young's modulus rises along with higher resin content. Its density increases as sintering temperature rises but decreases as temperature rises further to 1,300°C. The apparent porosity tends to increase with increasing sintering temperature. In addition, elevation of resin content and sintering temperature can reduce electrical resistance, and sintering temperature has greater impact. [ABSTRACT FROM AUTHOR]

Four new lanthanide(Ш) coordination polymers, [Ln( p-aminobenzoate)(DMF)(HCOO) (HO)] (Ln = Sm 1, Tb 2, Pr 3) and {[Pr(2,5-dcp)(CHCOO)(HO)]·1.5HO} ( 4) (DMF = N, N-dimethylformamide, 2,5-dcp = pyridine-2,5-dicarboxylate), have been synthesized by hydrothermal method. The structures are determined by the single-crystal X-ray diffraction. The four polymers all crystallize in the monoclinic space group P2/n. Polymers 1 and 2 are isostructural; both Sm ion of polymer 1 and Tb ion of polymer 2 are eight-coordinate. Although polymer 3 possesses the same asymmetric unit as polymers 1 and 2, the three are not isomorphous. The Pr ions in polymers 3 and 4 are nine-coordinate. In polymers 1, 2 and 3 the neighboring units are bridged by formyloxy and extend into infinite chains, which are connected by hydrogen bonds to form a hydrogen bond network. However, polymer 4 is bridged by pyridine-2,5-dicarboxylate and acetates to form an infinite 3D network. At room temperature, the IR, UV-Vis-NIR and emission spectra of the four polymers were measured and analyzed. The four polymers emit in the visible or NIR region. The luminescent properties are discussed. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) with bile duct tumor thrombi (BDTT) is a rare type of primary liver cancer, and its clinical and pathological characteristics remain to be defined.Aims: To investigate the clinical and pathological characteristics of HCC with BDTT.Methods: Among 676 HCC patients who underwent surgical treatment from Dec. 2002 to Dec. 2008 at the author's hospital, HCC with BDTT was identified in 20 patients. The clinical and pathological characteristics of the 20 patients were measured or analyzed retrospectively. The integrity of the involved bile duct was examined macroscopically and microscopically, the expression of liver stem cell markers was investigated by immunohistochemistry, and the Kaplan-Meier method was adopted for evaluating survival.Results: Among the 20 patients, the diameter of the primary tumor was less than 5 cm in 13 patients (range: 0.5-10 cm, mean 4.47±0.68 cm). Most of the primary tumors lacked an intact tumor capsule (15/20, 75%), had simultaneous blood vessel invasion (12/20, 60%), and were poorly differentiated (13/20, 65%). There was no evidence of bile duct wall infiltration by the tumor cells macroscopically or microscopically. The positive rate of the liver stem cell markers c-kit, CD90, CD133, and EpCAM was 90, 90, 85 and 85%, respectively. Postoperative overall survival rates at 1, 2, and 3 years were 73.1, 41.1, and 20.6%, respectively. The log-rank test showed that the overall survival rates were significantly worse for HCC patients with BDTT than for HCC patients without BDTT (P=0.016).Conclusions: HCC with BDTT has aggressive characteristics and the long-term prognosis is extremely dismal. [ABSTRACT FROM AUTHOR]

CD8+CD103+ tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+ TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+ TRMs are CD45RA−CCR7− effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+ TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+ TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+ TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+ TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8+CD103+ TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC. [ABSTRACT FROM AUTHOR]

Presents research which showed that [Na+]i regulates the function of N-methyl-D-aspartate (NMDA) receptors. Role of Na+ in the nervous system; Effects of increases in intracellular Na+ concentration; Increases in NMDA-receptor-mediated whole-cell currents and NMDA-receptor single-channel activity; Sensitivity of channels to Na+; Raising [Na+]i selectivity; Change in postsynaptic [Na+]i during neuronal activity.

In the present article, we report a novel colorimetric probe (TNT@MB) for the detection of the phosphate ion, which is based on the strong binding affinity between the phosphate ion and titanium dioxide nanotubes (TNTs). TNTs were synthesized from TiO2 nanoparticles by hydrothermal treatment. The obtained TNTs had an average length of 200 ± 50 nm and an average width of 12 ± 5 nm. TNT@MB was prepared by adsorbing methyl blue onto TNTs in acidic condition. The optimal synthesis conditions for TNT@MB consisted in having 0.05 g of TNTs react with 1 μmole of methyl blue at pH 2 for 90 min. TNTs and TNT@MB were characterized by UV–vis diffuse reflection spectroscopy, TEM, FTIR, and XPS. The phosphate-ion sensing behavior of TNT@MB was investigated by UV–visible spectroscopy. The phosphate-ion concentration linear range and detection limit of this method based on TNT@MB were 1–40 μM and 0.59 μM, respectively. A sample of lake water was used as a real sample, and analyte recovery rates were measured in the 102.5–103.6% range, with relative standard deviations below 5.6% (n = 3). We also found that this probe could be reused after regeneration in alkaline solution. These results indicate that as a colorimetric probe, TNT@MB has the advantages of being environmentally friendly, inexpensive, and simple to use, as well as giving rise to an easily observable color change. [ABSTRACT FROM AUTHOR]

Introduction: Real-world treatment of hepatitis C virus (HCV) infection is complicated by many factors that are controlled for in the rigorous clinical trial setting. The aim of the present study was to assess the efficacy of elbasvir/grazoprevir in a Veterans Affairs population with chronic HCV genotype 1b infection. Methods: This was a retrospective analysis of a cohort of patients aged ≥ 18 years with chronic HCV genotype 1b infection and ≥ 1 prescription of elbasvir/grazoprevir between February 1, 2016, and August 31, 2017. The primary analysis was conducted in the per-protocol population, which included all patients who had at least 11 weeks of treatment and had an available assessment for sustained virologic response (SVR) based on virologic data post–follow-up week 4. Results: The per-protocol population included 3371 patients. Overall, 97.3% of patients were male, 60.3% were black, and 85.5% were HCV treatment–experienced. Comorbidities in this population included hypertension (74.4%), history of alcohol use (55.7%), and depression (54.8%). In total, 97.5% of patients (3288/3371) achieved SVR. Among patient sub-groups, SVR was achieved by 96.0% (290/302) of those with chronic kidney disease stage 4/5, 97.8% (1527/1561) of those with a history of drug use, and 96.6% (831/860) of those with cirrhosis. No statistically significant differences were observed in the proportions of patients achieving SVR, regardless of age, race, HCV treatment history, viral load level, treatment regimen/duration, history of drug or alcohol use, HIV co-infection, or chronic kidney disease. Conclusion: Elbasvir/grazoprevir was highly effective in individuals with HCV genotype 1b infection in a large national Veterans Affairs clinical setting. [ABSTRACT FROM AUTHOR]

Post-grouting technology is widely used to increase the ultimate bearing capacity and decrease the settlement of bored piles. The post-grouting pile is designed according to double control criterion of bearing capacity and settlement, and there is a need to get an accurate load-settlement relationship of post-grouting pile. To get a better understanding on the response of combined side-and-tip grouting pile, the load transfer model of the combined side-and-tip grouting pile considering time-varying characteristics of slurry viscosity was established, and an iterative algorithm for the analysis on the load-settlement relationship of the combined side-and-tip grouting pile in layered soils was proposed in this paper. Comparisons between measured and computed results of three well-documented cases were made to verify the reliability of the calculation method. Furthermore, a parameter study was carried out to assess the influence of pile length, pile diameter and grouting parameters on the load-settlement relationship of single piles with different grouting types. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess whether postoperative adjuvant chemoimmunotherapy could lead to better clinical outcomes for high-risk patients with perihilar cholangiocarcinoma (pCCA). Methods: In the cohort study, we retrospectively reviewed patients who received surgical resection for pCCA with curative intent from January 2018 to December 2021 at the Sun Yat-sen Memorial Hospital. The patients at high risk for relapse were further analyzed. Among them, 20 patients received adjuvant chemoimmunotherapy, 28 patients received adjuvant chemotherapy, and 33 patients received surgery alone. The oncological outcomes and drug-associated adverse events were evaluated. Results: The 2-year overall survival (OS) rates in patients treated with adjuvant chemoimmunotherapy, adjuvant chemotherapy, and surgery alone were 80.0%, 49.4% and 22.6%, respectively. Univariable and multivariable Cox analyses showed that the treatment regimen and TNM stage were associated with adverse OS. Adjuvant chemoimmunotherapy led to an increase in OS compared with adjuvant chemotherapy [hazard ratio (HR) = 3.253; 95% confidence interval (CI) 1.072–9.870; P = 0.037] or surgery alone (HR = 7.560; 95% CI 2.508–22.785; P < 0.001). The median recurrence-free survival was 22.0 months for the adjuvant chemoimmunotherapy group, 17.0 months for the adjuvant chemotherapy group, and 13.2 months for the surgery alone group (P = 0.177); these differences were not significant. The chemoimmunotherapy group was associated with more frequent hematological side effects than the chemotherapy group, but the difference was not statistically significant. Conclusion: Postoperative adjuvant chemoimmunotherapy for resected pCCA patients showed improved OS compared with adjuvant chemotherapy or surgery alone, and further prospectively randomized controlled trials are necessary to validate these results. [ABSTRACT FROM AUTHOR]

Background and Aims: Hereditary hemochromatosis (HH) is associated with increased risk of hepatocellular carcinoma (HCC). However, HCC risk factors within this population and across various HFE genotypes remain unclear. Methods: We conducted a retrospective cohort study of patients with ≥ 1 HFE genotype test in the Veterans Health Administration. We followed patients until HCC, death, or 6/30/19. We calculated incidence rates (IRs) and used Cox proportional hazards models to estimate HCC risk. In patients with type-1 HH genotypes (C282Y/C282Y or C282Y/H63D), we examined risk factors for HCC. Results: We identified 5225 patients: 260 were C282Y/C282Y; 227 were C282Y/H63D; 436 were H63D heterozygous; 535 had other HFE mutations; 3767 without mutation. IR for C282Y/C282Y homozygotes (5.59/1000 PYs) and C282Y/H63D compound heterozygotes (4.12/1000 PYs) were significantly higher than controls (0.92/1000 PYs) with adjusted hazard ratio (adj HR), 95% CI 8.80, 4.17–18.54; and 5.25, 2.24–12.32, respectively. HCC risk was higher in H63D heterozygote than controls (adj HR = 2.82, 95% CI 1.21–6.58); cases were related to non-alcoholic fatty liver disease. Among patients with HH, age ≥ 65 (adj HR = 2.2, 95% CI 0.47–10.27), diabetes (adj HR 3.74, 95% CI 1.25–11.20) and high baseline aspartate-aminotransferase to platelet ratio-index (APRI, adj HR = 3.91, 95% CI 1.29–11.89) had higher risk. Among patients with high baseline ferritin, persistent ferritin > 250 ng/mL had higher risk. Conclusion: HCC risk was high in C282Y homozygous and C282Y/H63D patients. These HFE genotypes, older age, diabetes, high APRI/ferritin levels were associated with increased risk. While H63D heterozygous genotype was associated with HCC risk, this association might be due to metabolic factors. [ABSTRACT FROM AUTHOR]

To improve the structure and basic performance, carbon fibre-reinforced woodceramics with a laminated structure were prepared by using liquefied wood and carbon powder as matrix materials and carbon fibre as a reinforcing material through structure and process designs with the establishment of a unit structure model thereof. Basic performance tests indicated that the sintering temperature and content of liquefied wood played important roles. The apparent density first reduced, later increased and then decreased with increasing sintering temperature; the apparent porosity decreased with increasing liquefied wood content. Scanning electron microscopy showed that the woodceramics presented a clear laminated structure and tight joints between glassy carbon (GC) and the embedded carbon fibres. There was an interface layer found between the amorphous carbon and GC. Meanwhile, it still partially retained the natural structural characteristics of wood. Raman spectrum detection verified that raising the sintering temperature could increase the number of graphite crystallites and the orderliness of their arrangement. Transmission electron microscopy showed that the specimens formed at higher temperatures presented clear lattice fringes. In addition, the laminated structure and the application of reinforced carbon fibre greatly enhanced the bending strength, elastic modulus, and fracture toughness. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the different imaging features of contrast-enhanced multidetector-row-computed tomography (MDCT) for distinguishing between silicosis and tuberculosis involving the mediastinal lymph nodes. Methods: 86 silicosis patients and 61 tuberculosis patients with mediastinal lymphadenopathy based on contrast-enhanced MDCT were included. The enhanced patterns, anatomical distribution and calcification features of the enlarged lymph nodes were retrospectively compared between the groups using the Pearson chi-square test or Fisher's exact test. Results: Homogeneous enhancement of the mediastinal lymph nodes was more commonly observed in silicosis (94.2%, 81/86) than in tuberculosis (19.7%, 12/61). Peripheral enhancement was more frequent in tuberculosis (n = 44, 72.1%) than in silicosis involving the mediastinal lymph nodes (n = 1, 1.2%), and multilocular appearance was more frequent in TB than in silicosis. Tuberculosis was more likely to affect regions 1R, 2R, 2L, 3A, 5 and 6 than silicosis (all p < 0.05), especially region 2R. Calcification of the lymph nodes was more common in the silicosis group than in tuberculosis group. The sensitivity, specificity, and accuracy of silicosis with lymphadenopathy with homogeneous enhanced pattern were 94.2%, 80.3% and 88.4%, respectively. The sensitivity, specificity, and accuracy of tuberculosis lymphadenopathy with peripheral enhanced pattern were 72.1%, 98.8%, and 87.7%, respectively. Conclusion: The predominant enhanced patterns, anatomical distribution, and calcification features of mediastinal lymph nodes were different between tuberculosis and silicosis. These radiographic features might help differentiate tuberculosis from silicosis, which provides imaging information for the differential diagnosis of the two diseases in a clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: To search for a new radiographic view/projection of the acetabular anterior column to provide a safe guide for percutaneous screw placement for acetabular fractures. Materials and methods: Eight pelvic specimens taken from normal adult cadavers were positioned in a supine position on the operating table. First, the ipsilateral ilium-oblique view of the observed side was obtained on C-arm fluoroscopy by tilting the C-arm approximately 35° toward the contralateral hip joint. Then, the tilting angle of the C-arm was changed gradually until an oval track image (acetabular anterior column axial view) appeared. The oval shadow was clear only in one position as the angle of the C-arm was changed toward the caudal side of the operating table. A guide pin was put on the skin of the cadaver, and the location and tilting direction of the guide pin were adjusted under C-arm fluoroscopy until the pin's shadow became a point in the center of the oval track. Then, the guide pin was inserted into the bone using a battery-powered drill. The degree of inclination of the guide pin in the cadaver in the frontal and sagittal planes was measured using computed tomography (CT). Results: Axial views of the anterior column were found successfully in all of the pelvic specimens, and the guide pins were inserted accurately into the acetabular anterior column under C-arm fluoroscopic guidance. On the CT-reconstructed image, the average degree of angle between the guide pin and the sagittal plane was 33.6° (range 29.6°-36.5°). The average angle between the guide pin and the transverse plane was 59.1° (range 56.4°-63.2°). Conclusion: This axial view of the acetabular anterior column is a novel X-ray projection which provides an optimal method for guiding percutaneous insertion of anterior column screws for acetabular fractures. [ABSTRACT FROM AUTHOR]

Beauveria bassiana is a filamentous ascomycete that is pathogenic towards a broad host range of insect targets and is increasingly serving as a model for examining fungal development and host-pathogen interactions. B. bassiana displays a prohibitive level of resistance against many current fungal and/or yeast selection markers including hygromycin, neomycin, and zeocin. A genetic transformation system for B. bassiana based upon the use of a sulfonylurea resistance cassette derived from the Magnaporthe grisea, acetolactate synthase gene ( sur) was developed. The transformation frequency ranged from 100–150 transformants per microgram DNA/108 cells and Southern blot analysis indicated that the plasmid vector was randomly integrated into the genome of B. bassiana. In addition, a construct bearing the sur gene and the enhanced green fluorescent protein gene egfp as a visual marker was used to successfully transform B. bassiana. Over 95% of the transformants retained the sulfonylurea resistance phenotype under non-selective conditions. The described transformation method increases opportunities for the genetic manipulation of B. bassiana. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. Methods: We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. Results: PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5 years) of PanNETs after curative resection (P = 0.019, P < 0.001, and P < 0.001, respectively). Using these factors, we established a novel risk factor panel (R-panel), which predicted early recurrence (P < 0.001, HR = 15.02, 95% CI 5.76–39.19). Predictive accuracy of this R-panel was favorable, with a C-index of 0.853, higher than AJCC TNM staging (0.713). We further built an integrated staging system combining R-panel scoring and TNM staging, which improved predictive probability of TNM staging. Finally, we showed that adjuvant therapy with long-acting somatostatin analogs (SSAs) significantly reduced postoperative recurrence (P < 0.001) and prolonged long-term survival (P = 0.021) in patients with the above risk factors. Conclusion: We identified a novel risk factor panel, which includes PanNET G3, pancreatic duct dilatation, and perineural invasion; this panel predicted early recurrence of PanNETs after curative resection. Patients with these risk factors can benefit from adjuvant therapy with SSAs. [ABSTRACT FROM AUTHOR]

Background: There lacks an ideal model for accurately predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). This study aimed at developing a nomogram with high accuracy in predicting CR-POPF after PD. Methods: A total of 1182 patients undergoing PD in the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU, n = 762) and Fudan University Shanghai Cancer Center (FUSCC, n = 420) between January 2010 and May 2018 were enrolled. The patients from FAHSYSU were assigned as testing cohort, and those from FUSCC were used as external validation cohort. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors for CR-POPF. Nomogram was developed on the basis of significant predictors. The performance of nomogram was evaluated by area under receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis. Results: In testing cohort, 87 out of 762 patients developed CR-POPF. Three predictors were significantly associated with CR-POPF, including body mass index ≥24.0 kg/m2, pancreatic duct diameter <3 mm, and drainage fluid amylase on postoperative day 1 ≥2484 units/L (all p ≤ 0.001). Prediction of nomogram was accurate with AUC of 0.934 (95% confidence interval [CI]: 0.914–0.950) in testing cohort and 0.744 (95% CI: 0.699–0.785) in external validation cohort. The predictive accuracy of nomogram was better than that of previously proposed fistula risk scores both in testing and external validation cohort (all p < 0.05). Conclusions: The novel nomogram based on three easily available parameters could accurately predict CR-POPF after PD. It would have high clinical value due to its accuracy and convenience. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease mediated by monocyte infiltration and cholesterol deposition into the subendothelial area, resulting in foam cell development. Probiotics are live bacteria that are beneficial for health when administered orally in adequate amounts. In this study, 8-week-old atherosclerosis-prone apolipoprotein E-deficient (ApoE−/−) mice were fed with or without Lactobacillus plantarum ATCC 14917 per day for 12 weeks. Serum was collected to analyse the lipid profile, oxidative status and proinflammatory cytokines. The heart was isolated to quantify the atherosclerotic lesion size in the aortic arch. Quantitative real-time polymerase chain reaction was performed to determine the expression levels of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in the aorta. The proteins extracted from the aorta were used for Western blot analysis to assess the expression levels of nuclear factor kappa B (NF-κB) and inhibitor of NF-κB (IκBα). The composition of gut microbiota was also examined through high-throughput sequencing. Results showed that the daily consumption of L. plantarum ATCC 14917 had no effect on body weight and lipid profile. L. plantarum ATCC 14917 treatment significantly inhibited atherosclerotic lesion formation. In addition, the oxLDL, MDA, TNF-α and IL-1β levels were significantly reduced, whereas the SOD level was induced in the bacteria + high-fat diet group. Furthermore, the administration of L. plantarum ATCC 14917 significantly attenuated IκBα protein degradation and inhibited the translocation of P65 subunits of NF-κB. L. plantarum ATCC 14917 treatment also modulated the composition of gut microbiota in ApoE−/− mice. Our findings showed that L. plantarum ATCC 14917 supplementation decreases the progression of atherosclerotic lesion formation by alleviating the inflammatory process and lowering oxidative stress. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the efficacy of vildagliptin as add-on therapy to short-term continuous subcutaneous insulin infusion (CSII) with CSII monotherapy in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods: A total of 200 hospitalized patients with inadequately controlled T2DM were randomized into groups, with one group receiving CSII monotherapy (CSII group, n =100) and the other group receiving CSII plus vildagliptin as add-on (CSII + Vig group, n = 100). Of these, 191 completed the 7-day trial (CSII group, n = 99; CSII + Vig group, n = 92) and included in the analysis. The glycemic control and variability of the patients were measured using all-day capillary blood glucose (BG) monitoring. Weight and fasting C-peptide levels were evaluated before and after the interventions. Results: Mean BG concentrations during the whole treatment period were lower and the time to reach target BG was reduced in the CSII + Vig group compared with the CSII group (9.89 ± 3.37 vs. 9.46 ± 3.23 mmol/L, P < 0.01; 129 ± 4 vs. 94 ± 5 h, P < 0.01, respectively). Similarly, the indicators of glycemic variability, namely the standard deviation of BG and the largest amplitude of glycemic excursion, were significantly decreased in the CSII + Vig group compared with the CSII group (2.68 ± 1.05 vs. 2.39 ± 1.00 mmol/L, P < 0.01; 7.19 ± 2.86 vs. 6.23 ± 2.73 mmol/L, P < 0.01, respectively). Conclusions: Short-term CSII with vildagliptin as add-on therapy may be an optimized treatment for hospitalized patients with T2DM compared with short-term CSII monotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-related cognitive impairments in breast cancer patients were usually reported through cognitive questionnaires or scales which may be subjective and insensitive. This study is to assess the effect of chemotherapy on cognitive function in breast cancer patients stratified by age using objective electrophysiological measure, the P300 component of event-related potentials (ERPs) with a large sample size.Methods: Totally, 529 primary breast cancer patients, including 178 cases at initial diagnosis stage and before chemotherapy (Group1), 167 cases during chemotherapy (Group2), and 184 cases post chemotherapy and during follow-up period (Group3), were examined with ERPs (P300 component) to assess the effect of chemotherapy on their cognitive function.Results: There were significant differences of P300 latency in Group2 (364.74 ± 15.73 ms) and Group3 (364.02 ± 17.12 ms, mean follow-up period of 2.42 years) compared with Group1 (355.13 ± 19.47 ms, P < 0.001), respectively. With further age stratification: in patients of < 50 years, P300 latency was significantly prolonged in Group2 and Group3 compared with Group1 (P < 0.001), respectively; in patients of 50-59 years, P300 latency was significantly prolonged in Group2 compared with Group1 (P < 0.05), but without difference in Group1 and Group3 (P>0.05); In patients of ≥ 60 years, there were no differences of P300 latency among three the groups (P>0.05).Conclusions: It is first suggested by our objective detection data that the side effect of chemotherapy on cognitive functions in breast cancer patients may decrease with age. Electrophysiological cognitive impairments mainly occur in younger breast cancer patients undergoing chemotherapy and would last for years after chemotherapy, which highlights the importance of early intervention for those patients, especially in younger patients. [ABSTRACT FROM AUTHOR]

Background: With advent of direct-acting antiviral agents (DAA), hepatitis C virus (HCV) treatment is dramatically increasing. Although few studies reported rates of hepatocellular carcinoma (HCC) recurrence following DAA treatment, there have been no studies that followed sufficient number of DAA-treated patients after successful HCC treatment to examine HCC recurrence.Methods: We conducted a cohort study of HCV+ patients who had successfully treated HCC before initiating DAAs. We conducted medical record reviews to confirm HCC diagnosis, treatment, and remission prior to DAA initiation, and subsequent HCC recurrence. We calculated HCC recurrence rate and examined the recurrent tumor characteristics. We used Cox proportional hazard model to identify factors associated with HCC recurrence.Results: We identified 264 HCV+ patients who received DAAs after an average of 30.9 (20.6) months following HCC treatment. HCC recurred in 26.1% patients during 23.3 (9.8) months follow-up, at a rate of 0.38 [0.30, 0.48] per 1000 person-month. Most (82.3%) recurrent HCC were early stage. Receiving non-curative treatment for HCC was associated with a higher risk of recurrence than curative treatment (HRadj = 2.06, [1.24, 3.40]). The risk of HCC recurrence decreased with longer duration between HCC treatment completion and DAA initiation (HRadj = 0.97, [0.95, 0.99] per additional month). Compared with patients who achieved sustained virological response (SVR), those without SVR had significantly increased risk of HCC recurrence (HRadj = 4.17, [1.48, 11.75]).Conclusions: We conclude that most HCV+ patients with HCC benefit from DAA treatment; however, timing of DAA initiation after HCC treatment should be carefully considered. [ABSTRACT FROM AUTHOR]

In this note, we study the contributions from the S-wave resonances, f 0 (980) and f 0 (1500) , to the B s 0 → ψ (3770) π + π - decay by introducing the S-wave π π distribution amplitudes within the framework of perturbative QCD approach. Both the resonant and the non-resonant contributions are contained in the scalar form factor in the S-wave distribution amplitude Φ π π S . Since the vector charmonium meson ψ (3770) is a S–D wave mixed state, we calculate the branching ratios of S-wave and D-wave, respectively, and the results indicate that f 0 (980) is the main contribution of the considered decay, and the branching ratio of the ψ (2 S) mode is in good agreement with the experimental data. We also take the S–D mixed effect into the B s 0 → ψ (3686) π + π - decay. Our calculations show that the branching ratio of B s 0 → ψ (3770) (ψ (3686)) π + π - can be at the order of 10 - 5 , which can be tested by the running LHCb experiments. [ABSTRACT FROM AUTHOR]

A powerful technique to detect bone biomarkers has been developed for assessment of osteoporosis at the early stage. Two-dimensional multilayered gold-nanoparticle thin film (MTF-AuNPs) was demonstrated as a promising test platform for detection of bone biomarker, hydroxyproline (HYP), measured by surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). With strong surface plasmon resonance and excellent homogeneity, facilely prepared, highly ordered, and large-scale MTF-AuNPs revealed high sensitivity of HYP in the SALDI-MS measurement without additional matrixes, such as α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB). Furthermore, the mass spectrum of HYP with MTF-AuNPs was significantly improved in signal intensity enhancement, background noise reduction, and signal-to-noise ratio amplification. The excellent reproducibility of HYP spectra with only 9.3% relative signal variation could be attributed to MTF-AuNPs' high absorbance at a wavelength of 337 nm, low heat capacity, superior thermal conductivity, and outstanding homogeneity. The calibration curve showed high linear correlation between mass spectrum intensity and HYP concentration in the range of 1 to 100 μM, covering the whole level in healthy people and osteoporosis patients. In particular, the serum sample was directly deposited onto the MTF-AuNP sample substrate without any pretreatment and its HYP concentration was then successfully determined. We believe that the combination of SALDI-MS and MTF-AuNP sample substrates would be a potential approach for bone biomarker detection in the osteoporosis risk assessment. [ABSTRACT FROM AUTHOR]

We aimed to systematically evaluate the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases. Studies were searched in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases up to October 2018. There was no restriction for language and age. Prospective studies examining the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of eligible studies. Stata 15.1 and Meta-DiSc 1.4 software were used for data analysis. Eleven studies fulfilled the inclusion criteria (677 patients, 229 patients with bacterial infection, and 448 without infection). The pooled sensitivity and specificity of nCD64 were 89% (95% confidence interval (CI) 82–93) and 94% (95% CI 91–96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 14.9 (95% CI 9.3–23.8) and 0.12 (95% CI 0.07–0.20), respectively. The diagnostic odds ratio and area under the summary receiver operating characteristic curve were 123 (95% CI 53–283) and 0.97 (95% CI 0.95–0.98), respectively. The univariate meta-regression analysis showed that region, type of disease, antibiotic therapy, and presentation of nCD64 measurement results were responsible for the heterogeneity. The Deeks' funnel plot asymmetry test showed that there was no publication bias (p = 0.15). nCD64 has a good overall diagnostic performance for differentiating infection from disease flare in patients with autoimmune diseases. Further studies are needed to confirm the optimized cutoff value. [ABSTRACT FROM AUTHOR]

Iron overload is a common pathophysiological state underlying many diseases that has a detrimental influence on cells. The protective effects of Dexmedetomidine (Dex), a high selective alpha-2-adrenoceptor agonist, have been revealed through many experimental models, whereas no study reports its effects on an iron overload model. To elucidate these effects, we used FeCl2 with or without Dex to treat SH-SY5Y cells for 24 h and then detected indicators of oxidative stress, inflammation and apoptosis and investigated possible mechanisms further. After treatment with FeCl2 for 24 h, cell viability decreased in a dose dependent manner, and Dex promoted cell survival in FeCl2 incubation, also in a dose-dependent manner. Compared with the FeCl2 group, 20 µM Dex significantly attenuated ROS accumulation, reduced pro-inflammatory cytokine expression, and inhibited apoptosis. Furthermore, 20 µM concentration of Dex remarkably downregulated the expression of pro-apoptotic protein and activation of caspase 3 while increasing anti-apoptotic protein expression. Additionally, Dex also effectively suppressed the expression of NF-κB and its activation. In conclusion, Dex exerted anti-oxidative stress, anti-inflammation, and anti-apoptosis effects on FeCl2-treated SH-SY5Y cells, possibly by inhibiting NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Background and Aim: HOX transcript antisense intergenic RNA (HOTAIR) is a relatively well-understood RNA, which plays a central role in the pathogenesis of various tumors. The aim of the present study was to investigate the effect by which HOTAIR acts to influence the biological processes of colorectal cancer (CRC) through p21.Methods: Reverse transcription quantitative polymerase chain reaction and Western blot methods were employed to provide verification regarding the changes in HOTAIR, PCNA, Ki67, p21, cyclin E, and CDK2 among the CRC tissues and cells. The correlation between the clinicopathological characteristics of patients and expression of HOTAIR and p21 was subsequently evaluated, followed by an analysis into the effects of HOTAIR on the biological processes of M5 cells.Results: HOTAIR was found to be expressed at high levels, while p21 was determined to be at a low level among both the CRC tissues and the CRC cell lines. The expressions of HOTAIR and p21 were determined to be related to lymph node metastasis, tumor node metastasis, Dukes staging, distant metastases, histological types, and the degree of differentiation. Cells transfected with HOTAIR siRNA displayed inhibited rates of proliferation, invasion, and migration, as well as decreased cyclin E and CDK2, while apoptosis and p21 were increased.Conclusion: The principal findings demonstrated that down-regulation of HOTAIR elicits an inhibitory effect on proliferation, invasion, and migration, while promoting the apoptosis of CRC cells through the up-regulation of p21. We believe that HOTAIR could represent a novel target for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Recent studies have indicated a protective role of physiological autophagy in ischemic heart disease. However, the underlying mechanisms of autophagy regulation after ischemia are poorly understood. Exosomes are nano-sized vesicles released from cells that play critical roles in mediating cell-to-cell communication through the transfer of microRNAs. In this study, we observed that miR-30a was highly enriched in exosomes from the serum of acute myocardial infarction (AMI) patients in vivo and culture medium of cardiomyocytes after hypoxic stimulation in vitro. We also found that hypoxia inducible factor (HIF)-1α regulates miR-30a, which efficiently transferred via exosomes between cardiomyocytes after hypoxia. Inhibition of miR-30a or release of exosomes increased the expression of the core autophagy regulators beclin-1, Atg12, and LC3II/LC3I, which contributed to maintaining the autophagic response in cardiomyocytes after hypoxia. Taken together, the present study showed that exosomes from hypoxic cardiomyocytes regulate autophagy by transferring miR-30a in a paracrine manner, which revealed a new pathway of autophagy regulation that might comprise a promising strategy to treat ischemic heart disease. Key messages: [ABSTRACT FROM AUTHOR]

Recently, our group has developed a therapeutic hypertensive vaccine against angiotensin (Ang) II type 1 receptor (AT1R) named ATRQβ-001. To explore its potential effectiveness on streptozotocin-induced diabetic nephropathy, male Sprague Dawley rats were randomly divided into two groups: a control and a diabetic model. After 1 week, the diabetic rats were divided into four subgroups (each with 15 rats) for 14-week treatments with saline, olmesartan, ATRQβ-001, and Qβ virus-like particle (VLP), respectively. In addition to lower blood pressure, ATRQβ-001 vaccination ameliorated biochemical parameter changes of renal dysfunction, mesangial expansion, and fibrosis through inhibiting oxidative stress, macrophage infiltration, and proinflammatory factor expression. Furthermore, ATRQβ-001 vaccination suppressed renal Ang II-AT1R activation and abrogated the downregulation of angiotensin-converting enzyme 2-Ang (1-7), similar to olmesartan treatment, while no obvious feedback activation of circulating or local renin-angiotensin system (RAS) was only observed in vaccine group. In rat mesangial cells, the anti-ATR-001 antibody inhibited high glucose-induced transforming growth factor-β1 (TGF)-β1/Smad3 signal pathway. Additionally, no significant immune-mediated damage was detected in vaccinated animals. In conclusion, the ATRQβ-001 vaccine ameliorated streptozotocin-induced diabetic renal injury via modulating two RAS axes and inhibiting TGF-β1/Smad3 signal pathway, providing a novel, safe, and promising method to treat diabetic nephropathy. Key messages: [ABSTRACT FROM AUTHOR]

Purpose: Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by F-FDG PET/CT in patients with resectable PDAC. Methods: Included in the study were 122 PDAC patients who received preoperative F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). Results: MTV and TLG were significantly associated with baseline serum CA19-9 level ( P = 0.001 for MTV, P < 0.001 for TLG) and tumour size ( P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size ( P < 0.001 for all). Conclusion: MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. [ABSTRACT FROM AUTHOR]

Objective: To explore the characteristic expression of endoplasmic reticulum (ER) stress protein in antigen-induced arthritis models and the role of ER stress in arthritis. Methods: Effective animal models of rheumatoid arthritis in rabbits and rats were induced by methylated bovine serum albumin and Freund's complete adjuvant. Pathological changes were assessed by magnetic resonance imaging and histological analysis. The expression and localization of ER stress proteins in synovium and peritoneal macrophages (PMΦ) were analyzed by double immunofluorescence staining. RT-PCR was performed to detect mRNA expression of ER stress-related genes. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in synoviocytes were measured by RT-PCR and radioimmunoassay. Results: We found that the ER stress marker BiP was highly up-regulated in arthritis synovium and extensively expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS). The expression of the pro-apoptotic factor CHOP/GADD153 was slightly elevated in inflammatory synovium and mainly localized in FLS, but insignificant in MLS. Unexpectedly, increased expression of CHOP was observed in PMΦ in arthritis rats. Likewise, cleaved caspase-3 was rarely expressed in MLS. In addition, induction of ER stress by tunicamycin resulted in significantly increased expression of pro-inflammatory molecules such as IL-1β and TNF-α in cultured inflammatory FLS. Conclusion: Differential activation of the ER stress proteins in synovium MLS may contribute to the resistance of synoviocytes to ER stress-induced apoptosis. Furthermore, ER stress is a potential mediator of arthritis inflammation. [ABSTRACT FROM AUTHOR]

The risk of antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is a major obstacle for the development of dengue vaccine candidates. Here, we described a novel approach for assessment of ADE by measuring DENV nonstructural protein 1 (NS1) production in culture supernatants with Fcγ receptor-expressing K562 cells in ELISA format (ELISA-ADE). Enhancing activities quantified by measurement of kinetics of NS1 production were in a good agreement with the results of the virus titration assay. In conjunction with the previously established enzyme-linked immunospot-based micro-neutralization test (ELISPOT-MNT) in 96-well format, the observable dose-response profiles of enhancing and neutralizing activities against all four DENV serotypes were produced with two flaviviral envelope cross-reactive monoclonal antibodies and four primary DENV-1-infected human sera. The simple high-throughput ELISA-ADE assay offers advantages for quantitative measurement of infection enhancement that can potentially be applied to large-scale seroepidemiological studies of DENV infection and vaccination. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium (Na) and potassium (K) channels have been found to be regulated by Src family kinases (SFKs). However, how these channels are regulated by SFKs in cochlear spiral ganglion neurons (SGNs) remains unknown. Here, we report that altering the activity of endogenous SFKs modulated voltage-gated Na, but not K, currents recorded in embryonic SGNs in culture. Voltage-gated Na current was suppressed by inhibition of endogenous SFKs or just Src and potentiated by the activation of these enzymes. Detailed investigations showed that under basal conditions, SFK inhibitor application did not significantly affect the voltage-dependent activation, but shifted the steady-state inactivation curves of Na currents and delayed the recovery of Na currents from inactivation. Application of Src specific inhibitor, Src40-58, not only shifted the inactivation curve but also delayed the recovery of Na currents and moved the voltage-dependent activation curve towards the left. The pre-inhibition of SFKs occluded all the effects induced by Src40-58 application, except the left shift of the activation curve. The activation of SFKs did not change either steady-state inactivation or recovery of Na currents, but caused the left shift of the activation curve. SFK inhibitor application effectively prevented all the effects induced by SFK activation, suggesting that both the voltage-dependent activation and steady-state inactivation of Na current are subjects of SFK regulation. The different effects induced by activation versus inhibition of SFKs implied that under basal conditions, endogenously active and inactive SFKs might be differentially involved in the regulation of voltage-gated Na channels in SGNs. [ABSTRACT FROM AUTHOR]

A hepatic artery aneurysm is an unusual but life-threatening hepatobiliary complication occurring in patients with systemic lupus erythematosus (SLE), and early diagnosis and treatment of this complication are essential. A 31-year-old man with SLE presented with recurring epigastric pain and jaundice for 2 months; he was diagnosed with choledocholithiasis and underwent surgery. Hemobilia was found intraoperatively, and two hepatic artery aneurysms were identified in the left lateral lobe during postoperative arteriography. Major hemobilia occurred 6 days after the operation, and the patient was immediately treated with selective embolization of the hepatic artery. However, the major hemobilia recurred 2 days later, and he was treated with a left lateral lobectomy and ligation of the proximal hepatic artery. The patient recovered uneventfully and is in good condition. A histological analysis revealed small- and medium-sized arteritis as well as hepatic artery aneurysm. Systemic lupus erythematosus complicated by a hepatic artery aneurysm should be considered in the differential diagnosis of patients showing symptoms of abdominal pain, jaundice, or gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Previous studies have shown that Csk plays critical roles in the regulation of neural development, differentiation and glutamate-mediated synaptic plasticity. It has been found that Csk associates with the NR2A and 2B subunits of N-methyl-D-aspartate receptors (NMDARs) in a Src activity-dependent manner and serves as an intrinsic mechanism to provide a 'brake' on the induction of long-term synaptic potentiation (LTP) mediated by NMDARs. In contrast to the NR2A and 2B subunits, no apparent tyrosine phosphorylation is found in the NR1 subunit of NMDARs. Here, we report that Csk can also associate with the NR1 subunit in a Src activity-dependent manner. The truncation of the NR1 subunit C-tail which contains only one tyrosine (Y837) significantly reduced the Csk association with the NR1-1a/NR2A receptor complex. Furthermore, we found that either the truncation of NR2A C-tail at aa 857 or the mutation of Y837 in the NR1-1a subunit to phenylalanine blocked the inhibition of NR1-1a/NR2A receptors induced by intracellular application of Csk. Thus, both the NR1 and NR2 subunits are required for the regulation of NMDAR activity by Csk. [ABSTRACT FROM AUTHOR]

The whitefly Bemisia tabaci (Gennadius) is an important agricultural insect pest worldwide. The B and Q biotypes are the two most predominant and devastating biotypes prevalent across China. However, there are few studies regarding the occurrence of the Q biotype in Fujian Province, China, where high insecticide resistance has been reported in the B biotype. Differences in some biological characteristics between the B and Q biotypes, especially insecticide resistance, are considered to affect the outcome of their competition. Extensive surveys in Fujian revealed that the B biotype was predominant during 2005-2014, whereas the Q biotype was first detected in some locations in 2013 and widely detected throughout the province in 2014. Resistance to neonicotinoids (that have been used for more than 10 years) exhibited fluctuations in open fields, but showed a continual increasing trend in protected areas. Resistance to lambda-cyhalothrin, chlorpyrifos, and abamectin exhibited a declining trend. Resistance to novel insecticides, such as nitenpyram, pymetrozine, sulfoxaflor, and cyantraniliprole, in 2014 was generally below a moderate level. A decline in insecticide resistance in the B biotype and the rapid buildup of protected crops under global temperature increase may have promoted the establishment of the Q biotype in Fujian. [ABSTRACT FROM AUTHOR]