To understand the mechanism(s) of age‐dependent outcomes of hepatitis B virus (HBV) infection in humans, we previously established an age‐related HBV mouse model in which 6‐week‐old (N6W) C3H/HeN ...mice exhibited virus tolerance whereas 12‐week‐old (N12W) counterparts presented virus clearance. By investigating the hepatic myeloid cell dynamics in mice of these two ages, we aim to identify factors associated with HBV clearance. C3H/HeN mice were transfected with an HBV plasmid by hydrodynamic injection. Serum HBV markers were monitored weekly. Hepatic leucocyte populations and their cytokine/chemokine productions were examined at baseline, day 3 (D3), day 7 (D7), and day 14 after injection. C‐C chemokine receptor type 2 (CCR2) antagonist and clodronate (CLD) were respectively administered to N12W and N6W mice to study the roles of lymphocyte antigen 6 complex, locus C (Ly6C)+ monocytes and Kupffer cells (KCs) in viral clearance. N12W mice had a significantly higher number of TNF‐α–secreting Ly6C+ monocytes and fewer IL‐10–secreting KCs at D3 in the liver than their younger N6W counterparts after HBV transfection. In addition, the elevated number of interferon‐γ+TNF‐α+ CD8+ T cells at D7 was only seen in the older cohort. The enhanced Ly6C+ monocyte induction in N12W mice resulted from elevated C‐C motif chemokine ligand 2 (CCL2) secretion by hepatocytes. CCR2 antagonist administration hampered Ly6C+ monocyte recruitment and degree of KC reduction and delayed HBV clearance in N12W animals. Depletion of KCs by CLD liposomes enhanced Ly6C+ monocyte recruitment and accelerated HBV clearance in N6W mice. Conclusions: Ly6C+ monocytes and KCs may, respectively, represent the resistance and tolerance arms of host defenses. These two cell types play an essential role in determining HBV clearance/tolerance. Manipulation of these cells is a promising avenue for immunotherapy of HBV‐related liver diseases.
A wet-chemical method combined with spark plasma sintering was used to prepare W-0.5 wt% Y2O3 alloy. The W-0.5 wt% Y2O3 precursor was reduced at 800 °C for 4 h under different hydrogen flow rates of ...300, 400, 500, 600, and 700 ml/min. The reduced powder was analyzed by X-ray diffraction (XRD), laser particle size analyzer (LPSA), and scanning electron microscopy (SEM). An optimized process for reducing precursor was discussed. After sintering, the specimens were exposed to different laser beam irradiation energies (90, 120, 150, and 180 W) to simulate loads as expected for edge localized modes (ELMs). Top surface and cross-sectional morphology were observed by SEM, and the changes in hardness were evaluated. The changes in microstructural properties (i.e., Y2O3-particle distribution, crack propagation direction, depth of thermal shock effect, and grain size of the recrystallization region) after thermal shock were investigated.
This study explored the relationship between adolescents' emotional intelligence and the tendency to develop an eating disorder.
Senior high school students in Taiwan were recruited for the study. A ...3- part anonymous questionnaire measured demographic information, body weight satisfaction, and expectation of body weight. Students also completed the Adolescent Emotional Intelligence Scale and the Eating Disorders Attitude- 26 Test (EAT-26). Height and weight were also measured.
The mean of EAT-26 score was 8.66 ± 7.36, and 8.6% students were at high risk to develop eating disorders. Gender, body weight, body dissatisfaction and the expected body shape were significantly related to disturbed eating attitudes and behaviours. Scores of EAT-26 were positively correlated with emotional perception, emotional expression, and emotional application.
Disturbed eating behaviours exist among adolescents in Taiwan, and these behaviours may be related to emotional intelligence. However further studies with larger samples are needed.
Aconite alkaloids from the roots of Aconitum carmichaeli (Fuzi, in Chinese) have been investigated by rapid-resolution liquid chromatography coupled with time-of-flight mass spectrometry (TOFMS) in ...positive mode. With dynamic adjustment of the key role as fragmentor voltage in TOFMS, an efficient transmission of the ions was achieved to obtain the best sensitivity for providing the molecular formula for each analyte, and abundant fragment ions for structural information. Fifteen authentic standards isolated from Fuzi with various structures were first characterized by TOFMS, including diester-diterpenoid alkaloids (DDAs), monoester-diterpenoid alkaloids (MDAs), alkylol amine-diterpenoid alkaloids (ADAs), veatchine-type alkaloids and atisine-type alkaloids. Fragmentation rules and key diagnostic fragment ions have been summarized, and possible pathways of fragmentation have been proposed. By accurate mass measurements within 5 ppm error for each ion, 30 C(19)-diterpenoid alkaloids including 10 DDAs, 3 MDAs, 9 ADAs and 8 other type alkaloids, and 8 C(20)-diterpenoid alkaloids including 4 veatchine-type alkaloids and 4 atisine-type alkaloids could be identified in a methanolic extract of Fuzi. Some isomers of aconite alkaloids were also differentiated. Based on the differences between their fragmentation pathways and special fragment ions, each type of aconite alkaloids was differentiated.
Background：Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies （especially for the treatment of B-cell chronic lymphocytic leukemia）.However,serious ...infectious complications frequently occur after treatment.The reason for increased infections postalemtuzumab treatment is unknown at this stage.We explore the effect ofalemtuzumab on intestinal intraepithelial lymphocytes （IELs） and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.Methods：Twelve male cynomolguses were randomly assigned to either a treatment or control group.The treatment group received alemtuzumab （3 mg/kg,intravenous injection） while the control group received the same volume of physiological saline.Intestinal IELs were isolated from the control group and the treatment group （on day 9,35,and 70 after treatment） for counting and flow cytometric analysis.Moreover,intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.Results：The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group （0.35 ± 0.07 × 10^8 and 1.35 ± 0.09 × 10^8,respectively; P 〈 0.05） and were not fully restored until day 70 after treatment.There were significant differences among four groups considering IELs subtypes.In addition,the proportion ofapoptotic IELs after alemtuzumab treatment was significantly higher than in the control group （22.01 ± 3.67 and 6.01 ± 1.42,respectively; P 〈 0.05）.Moreover,the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.Conclusions：Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model.The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment.Notably,intestinal barrier function may be disrupted after alemtuzumab treatment.
Recent studies have shown that induced expression of endogenous antioxidative enzymes thr- ough activation of the antioxidant response element/nuclear factor erythroid 2-related factor 2 （Nrf2） ...pathway may be a neuroprotective strategy. In this study, rat cerebral cortical neurons cultured in vitro were pretreated with 10 ktM curcumin or post-treated with 5 pM curcumin, respectively before or after being subjected to oxygen-glucose deprivation and reoxygenation for 24 hours. Both pretreatment and post-treatment resulted in a significant decrease of cell injury as indicated by propidium iodide/Hoechst 33258 staining, a prominent increase of Nrf2 protein expression as indicated by western blot analysis, and a remarkable increase of protein expression and enzyme activity in whole cell lysates of thioredoxin before ischemia, after ischemia, and after reoxygenation. In addition, post-treatment with curcumin inhibited early DNA/RNA oxidation as indicated by immunocytochemistry and increased nuclear Nrf2 protein by inducing nuclear accumulation of Nrf2. These findings suggest that curcumin activates the expression of thi- oredoxin, an antioxidant protein in the Nrf2 pathway, and protects neurons from death caused by oxygen-glucose deprivation in an in vitro model of ischemia/reperfusion. We speculate that pharmacologic stimulation of antioxidant gene expression may be a promising approach to neu- roprotection after cerebral ischemia.
<正>Objective:To investigate the prevalence and risk factors of bronchial asthma in the Li ethnic group in Hainan,China.Methods:This study employed a stratified random sample design using ...custom-designed questionnaires.Subjects with asthma-like symptoms were first identified by two rounds of surveys and then confirmed by respiratory physicians using pulmonary function test,bronchial dilation test and challenge test.Demographic data,information on family history of asthma,history of allergies,smoking habits,domestic cooking fuel and other potential risk factors were collected.Logistic regression was performed to evaluate risk factors for asthma.Results: The prevalence of asthma in the Li ethnic group was 3.38%,much higher than the national average level in China.Aging,agriculture industry(the rubber industry in particular),rural residence,family history of asthma,history of allergies,cold air,inhalation of dust and irritant gases,smoking,domestic cooking fuel and living environment were associated with increased risk of asthma.Conclusions:The high prevalence of asthma in the Li ethnic group highlights the importance of asthma prevention and treatment in this population.Risk factors indentified in this study warrant special attention.Elevating public awareness about asthma in local communities will benefit the prevention of the disease.
Continuous capture with affinity chromatography is one of the most important units for continuous manufacturing of monoclonal antibody (mAb). Due to the complexity of three‐column periodic ...counter‐current chromatography (3C‐PCC), three approaches (experimental, model‐based, and simplified approaches) were studied for process development and optimization. The effects of residence time for interconnected load (RT
C), breakthrough percentage of the first column for interconnected load (s) and feed protein concentration (c
0) on productivity and capacity utilization were focused. The model‐based approach was found superior to the experimental approach in process optimization and evaluation. Two phases of productivity were observed and the optimal RT
C for the maximum productivity was located at the boundary of the two phases. The comprehensive effects of the operating parameters (RT
C, s, and c
0) were evaluated by the model‐based approach, and the operation space was predicted. The best performance of 34.5 g/L/h productivity and 97.6% capacity utilization were attained for MabSelect SuRe LX resin under 5 g/L concentration at RT
C = 2.8 min and s = 87.5%. Moreover, a simplified approach was suggested to obtain the optimal RT
C for the maximum productivity. The results demonstrated that model‐assisted tools are useful to determine the optimum conditions for 3C‐PCC continuous capture with high productivity and capacity utilization.
Three‐column periodic counter‐current chromatography for continuous affinity capture was investigated and three approaches (experimental, model‐based, and simplified approaches) were compared to characterize the operating parameters for process optimization. Compared with the experimental approach, the model‐based approach was superior for high efficiency and accuracy, which provides a useful tool to evaluate the continuous process in a comprehensive way. A simplified approach was proposed as an alternative for the model‐based approach with less computational requirement and fast evaluation.
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