Hot Deformation Behavior and Microstructure Evolution Mechanisms of Ti6Al4V Alloy under Hot Stamping Conditions.

Through the study of the thermal rheological behavior of Ti6Al4V alloy at different temperatures (500 °C, 600 °C, 700 °C, and 800 °C) and different strain rates (0.1 s-1, 0.05 s-1, 0.01 s-1, and 0.005 s-1), a constitutive model was developed for Ti6Al4V alloy across a wide temperature range in the hot stamping process. The model's correlation coefficient reached 0.9847, indicating its high predictive accuracy. Hot processing maps suitable for the hot stamping process of Ti6Al4V alloy were developed, demonstrating the significant impact of the strain rate on the hot formability of Ti6Al4V alloy. At higher strain rates (>0.05 s-1), the hot processing of Ti6Al4V alloy is less prone to instability. Combining hot processing maps with hot stamping experiments, it was found that the forming quality and thickness uniformity of parts improved significantly with the increase in stamping speed. The phase composition and microstructures of the forming parts under different heating temperature conditions have been investigated using SEM, EBSD, XRD, and TEM, and the maximum heating temperature of hot stamping forming was determined to be 875 °C. The recrystallization mechanism in hot stamping of Ti6Al4V alloys was proposed based on EBSD tests on different sections of a hot stamping formed box-shaped component. With increasing deformation, the effect of dynamic recrystallization (DRX) was enhanced. When the thinning rate reached 15%, DRX surpassed dynamic recovery (DRV) as the dominant softening mechanism. DRX grains at different thinning rates were formed through both discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX), with CDRX always being the dominant mechanism.

Finite Element Simulation and Microstructural Evolution Investigation in Hot Stamping Process of Ti6Al4V Alloy Sheets.

Titanium alloy hot stamping technology has a wide range of application prospects in the field of titanium alloy part processing due to its high production efficiency and low manufacturing cost. However, the challenges of forming titanium alloy parts with large depths and deformations have restricted its development. In this study, the hot stamping process of a Ti6Al4V alloy box-shaped part was investigated using ABAQUS 2020 software. The thermodynamic properties of a Ti6Al4V alloy sheet were explored at different temperatures (400 °C, 500 °C, 600 °C, 700 °C, 800 °C) and different strain rates (0.1 s-1, 0.05 s-1, 0.01 s-1). In addition, the influence law of hot stamping process parameters on the minimum thickness of the formed part was revealed through the analysis of response surface methodology (RSM), ultimately obtaining the optimal combination of process parameters for Ti6Al4V alloy hot stamping. The experimental results of the hot stamping process exhibited a favorable correlation with the simulated outcomes, confirming the accuracy of the numerical simulation. The study on the microstructure evolution of the formed parts showed that grain refinement strengthening occurred in the part with large deformation, and the formed box-shaped parts exhibited a uniform and fine microstructure overall, demonstrating high forming quality. The achievements of the work provide important guidance for the fabrication of titanium alloy parts with large depths and deformations used in heavy industrial production.

MiRNA-338-3p Inhibits Neuroinflammation in the Corpus Callosum of LCV-LPS Rats Via STAT1 Signal Pathway.

Neuroinflammation is a common characteristic of intracranial infection (ICI), which is associated with the activation of astrocytes and microglia. MiRNAs are involved in the process of neuroinflammation. This study aimed to investigate the potential mechanism by which miR-338-3p negatively modulate the occurrence of neuroinflammation. We here reported that the decreased levels of miR-338-3p were detected using qRT-PCR and the upregulated expression of TNF-α and IL-1ß was measured by ELISA in the cerebrospinal fluid (CSF) in patients with ICI. A negative association between miR-338-3p and TNF-α or IL-1ß was revealed by Pearson correlation analysis. Sprague-Dawley (SD) rats were injected with LPS (50 µg) into left cerebral ventricule (LCV), following which the increased expression of TNF-α and IL-1ß and the reduction of miR-338-3p expression were observed in the corpus callosum (CC). Moreover, the expression of TNF-α and IL-1ß in the astrocytes and microglia in the CC of LCV-LPS rats were saliently inhibited by the overexpression of miR-338-3p. In vitro, cultured astrocytes and BV2 cells transfected with mimic-miR-338-3p produced less TNF-α and IL-1ß after LPS administration. Direct interaction between miR-338-3p and STAT1 mRNA was validated by biological information analysis and dual luciferase assay. Furthermore, STAT1 pathway was found to be implicated in inhibition of neuroinflammation induced by mimic miR-338-3p in the astrocytes and BV2 cells. Taken together, our results suggest that miR-338-3p suppress the generation of proinflammatory mediators in astrocyte and BV2 cells induced by LPS exposure through the STAT1 signal pathway. MiR-338-3p could act as a potential therapeutic strategy to reduce the neuroinflammatory response. Diagram describing the cellular and molecular mechanisms associated with LPS-induced neuroinflammation via the miR-338-3p/STAT1 pathway. LPS binds to TLRs on astrocytes or microglia to activate the STAT1 pathway and upregulate the production of pro-inflammatory cytokines. However, miR-338-3p inhibits the expression of STAT1 and reduces the production of inflammatory mediators.

Predicting the Popularity of Information on Social Platforms without Underlying Network Structure.

The ability to predict the size of information cascades in online social networks is crucial for various applications, including decision-making and viral marketing. However, traditional methods either rely on complicated time-varying features that are challenging to extract from multilingual and cross-platform content, or on network structures and properties that are often difficult to obtain. To address these issues, we conducted empirical research using data from two well-known social networking platforms, WeChat and Weibo. Our findings suggest that the information-cascading process is best described as an activate-decay dynamic process. Building on these insights, we developed an activate-decay (AD)-based algorithm that can accurately predict the long-term popularity of online content based solely on its early repost amount. We tested our algorithm using data from WeChat and Weibo, demonstrating that we could fit the evolution trend of content propagation and predict the longer-term dynamics of message forwarding from earlier data. We also discovered a close correlation between the peak forwarding amount of information and the total amount of dissemination. Finding the peak of the amount of information dissemination can significantly improve the prediction accuracy of our model. Our method also outperformed existing baseline methods for predicting the popularity of information.

Study on the Effect of the Pre-Forming of 22MnB5 Steel in Indirect Hot Stamping.

Based on the indirect hot-stamping test system, the effect of pre-forming on the microstructure evolution (grain size, dislocation density, martensite phase transformation) and mechanical properties of the blank in indirect hot stamping is systematically studied using ultra-high-strength steel 22MnB5. It is found that the average austenite grain size slightly decreases with the increase in pre-forming. After quenching, the martensite also becomes finer and more uniformly distributed. Although the dislocation density after quenching slightly decreases with the increase in pre-forming, the overall mechanical properties of the quenched blank are not greatly affected by pre-forming under the combined effect of the grain size and dislocation density. Then, this paper discusses the effect of the pre-forming volume on part formability in indirect hot stamping by manufacturing a typical beam part. According to the numerical simulations and experimental results, when the pre-forming volume increases from 30% to 90%, the maximum thickness thinning rate of the beam part decreases from 30.1% to 19.1%, and the final beam part has better formability and more uniform thickness distribution results when the pre-forming volume is 90%.

Investigation of the Hot Stamping-in-Die Quenching Composite Forming Process of 5083 Aluminum Alloy Skin.

Aluminum alloy has been used as the skin material for rail vehicles and automobiles to meet the requirements of environmental protection. The hot stamping-in-die quenching composite forming (HFQ) process is a promising technology to compensate for the poor formability of the aluminum alloy sheet at room temperature. In this paper, the high-temperature mechanical properties of 5083 aluminum alloy under various temperature (200 °C, 300 °C, 400 °C, 450 °C) and strain rate conditions (0.01 s-1, 0.10 s-1, 1.00 s-1) were investigated by uniaxial tensile tests. The finite element software of PAM-STAMP was employed to simulate the forming process of high-speed train skin. The effects of forming method and process parameters on the minimum thickness and springback of the skin were analyzed using the Response Surface Methodology (RSM). After parameter optimization, the forming experiment verified the simulation results and the test part met the quality requirements: the thickness above 3.84 mm and the springback within 1.1 mm. Mechanical properties of the sheet before and after HFQ were examined by uniaxial tensile tests at room temperature. It can be inferred from the comparison that the yield strength of the Al5083 sheet increases, but the elongation decreases from the HFQ process.

Association between Galectin-13 Expression and Eosinophilic Airway Inflammation in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) and asthma are chronic inflammatory diseases of the airways. Galectin-13 has recently been forwarded as a biomarker for airway eosinophilic inflammation in asthma. However, the association between galectin-13 and COPD remains unknown. To examine the changes in galectin-13 expression in acute exacerbations of COPD (AECOPD) and the stable phase of COPD and unveil the association between galectin-13 expression and eosinophilic inflammation in COPD, we measured plasma galectin-13 expression in different phases of COPD patients (n = 60, 44 AECOPD patients, and 16 stable COPD patients) and healthy controls (n = 15). Plasma levels of galectin-13 in 60 COPD patients were further analyzed and compared to systemic inflammation, airway eosinophilic inflammation, and lung function. The plasma galectin-13 level was markedly increased in subjects with AECOPD compared to stable COPD patients and healthy controls. Plasma galectin-13 levels in COPD subjects were positively correlated with serum CRP (rs = 0.46, p = 0.0003), peripheral blood eosinophilia count (rs = 0.57, p<0.0001), and FeNO (rs = 0.46, p = 0.0002). In addition, the level of galectin-13 was negatively correlated with FEV1 (rs = -0.43, p = 0.0001), FEV1 pred (%) (rs = -0.544, p<0.0001), as well as FEV1/FVC (rs = -0.46, p<0.0001). Multiple linear regression analysis suggested that plasma galectin-13 levels were affected by FEV1 pred (%), peripheral blood eosinophilia count, and FeNO. We concluded that galectin-13 levels were increased in COPD patients, and elevated galectin-13 expressions related to airway eosinophilic inflammation. Galectin-13 may facilitate the identification of COPD endotypes and may become a potential therapeutic target.

Theoretical Investigation of Forming Process of Aluminum Alloy Rail Vehicle Side Window.

With the vigorous development of rail transit trains around the world and the emergence of global environmental pollution and energy shortages, the world has an urgent need for manufacturing technology for lightweight aluminum alloy rail transit train components. This paper mainly studied the superplastic forming law of 5083Al for rail transit. Through the high-temperature tensile test and blowing forming experiments, the superplastic properties of 5083Al were determined. Based on this, the die design, finite element simulation, and forming experiment of the rail vehicle side window were carried out. In order to study the superplastic deformation behavior of industrial 5083Al under complex stress conditions, the influence of the depth, area ratio, and friction coefficient of the pre-forming die on the part thickness distribution is simulated. The side window is made of a high-strength 5083Al sheet in the form of bending at both ends to ensure the strength of the connection between the overall side window and the side wall skeleton. The variation law of the side wall forming height of 5083Al box-shaped parts was studied. The efficient manufacture of parts that meet quality standards was made possible by the optimization of the pressure profile. The microstructure changes of the material after superplastic forming were studied by Energy Dispersive Spectrometer (EDS) and Electron Backscattered Diffraction (EBSD).

Cadherin-26 Amplifies Airway Epithelial IL-4 Receptor Signaling in Asthma.

Activation of IL-4R (IL-4 receptor) signaling in airway epithelial cells leads to airway hyperresponsiveness and mucus overproduction in asthma. CDH26 (cadherin-26), a cadherin implicated in the polarization of airway epithelial cells, is upregulated in asthma. However, the role of CDH26 in asthma remains unknown. In this study, we demonstrated that Cdh26 deficiency significantly reduced airway mucus overproduction, airway hyperresponsiveness, and airway eosinophilia in a murine model of allergic airway disease. Interestingly, allergen-induced Il-4Rα upregulation in airway epithelium was markedly reduced in Cdh26-/- mice. In cultured human bronchial epithelial cells, CDH26 knockdown inhibited IL-13, a ligand for IL-4R; induced IL-4Rα and IL-13Rα1 (IL-13 receptor α1) upregulation; and suppressed downstream Jak1 (Janus kinase 1) and Stat6 (signal transducer and activator of transcription 6) phosphorylation. Moreover, CDH26 knockdown inhibited IL-13-induced MUC5AC and eosinophilic chemokine expression. These results suggest that CDH26 plays a key role in epithelial IL-4R signaling activation and downstream effectors. In contrast, CDH26 overexpression amplified IL-13-activated IL-4R signaling in BEAS-2B cells. In the airway epithelium of patients with asthma, IL-4Rα expression was elevated, and CDH26 was the only cadherin that was upregulated among 11 cadherin family members. CDH26 expression was strongly correlated with epithelial IL-4Rα and MUC5AC expression, sputum eosinophilia, and fractional exhaled nitric oxide in patients with asthma. Taken together, we identified CDH26 as a key regulator of epithelial IL-4R signaling in asthma and a potential therapeutic target for IL-4R-mediated allergic diseases.

Epithelial microRNA-30a-3p targets RUNX2/HMGB1 axis to suppress airway eosinophilic inflammation in asthma.

BACKGROUND: Type 2-high asthma is a prominent endotype of asthma which is characterized by airway eosinophilic inflammation. Airway epithelial cells play a critical role in the pathogenesis of asthma. Our previous miRNA profiling data showed that miR-30a-3p was downregulated in bronchial epithelial cells from asthma patients. We hypothesize that epithelial miR-30a-3p plays a role in asthma airway inflammation. METHODS: We measured miR-30a-3p expression in bronchial brushings of asthma patients (n = 51) and healthy controls (n = 16), and analyzed the correlations between miR-30a-3p expression and airway eosinophilia. We examined whether Runt-related transcription factor 2 (RUNX2) was a target of miR-30a-3p and whether RUNX2 bound to the promoter of high mobility group box 1 (HMGB1) by using luciferase reporter assay and chromatin immunoprecipitation (ChIP)-PCR. The role of miR-30a-3p was also investigated in a murine model of allergic airway inflammation. RESULTS: We found that miR-30a-3p expression were significantly decreased in bronchial brushings of asthma patients compared to control subjects. Epithelial miR-30a-3p expression was negatively correlated with parameters reflecting airway eosinophilia including eosinophils in induced sputum and bronchial biopsies, and fraction of exhaled nitric oxide in asthma patients. We verified that RUNX2 is a target of miR-30a-3p. Furthermore, RUNX2 bound to the promoter of HMGB1 and upregulated HMGB1 expression. RUNX2 and HMGB1 expression was both enhanced in airway epithelium and was correlated with each other in asthma patients. Inhibition of miR-30a-3p enhanced RUNX2 and HMGB1 expression, and RUNX2 overexpression upregulated HMGB1 in BEAS-2B cells. Intriguingly, airway overexpression of mmu-miR-30a-3p suppressed Runx2 and Hmgb1 expression, and alleviated airway eosinophilia in a mouse model of allergic airway inflammation. CONCLUSIONS: Epithelial miR-30a-3p could possibly target RUNX2/HMGB1 axis to suppress airway eosinophilia in asthma.

Decreased eosinophil counts and elevated lactate dehydrogenase predict severe COVID-19 in patients with underlying chronic airway diseases.

BACKGROUND: Several predictors of COVID-19 severity have been reported. However, chronic airway inflammation characterised by accumulated lymphocytes or eosinophils may affect the pathogenesis of COVID-19. METHODS: In this retrospective cohort study, we reviewed the medical records of all patients with laboratory-confirmed COVID-19 with chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma admitted to the Sino-French New City Branch of Tongji Hospital, a large regional hospital in Wuhan, China, from 26 January to 3 April. The Tongji Hospital Ethics Committee approved this study. RESULTS: There were 59 patients with chronic bronchitis, COPD and asthma. When compared with non-severe patients, severe patients were more likely to have decreased lymphocyte counts (0.6×109/L vs 1.1×109/L, p<0.001), eosinopaenia (<0.02×109/L; 73% vs 24%, p<0.001), increased lactate dehydrogenase (LDH) (471.0 U/L vs 230.0 U/L, p<0.001) and elevated interleukin 6 level (47.4 pg/mL vs 5.7 pg/mL, p=0.002) on admission. Eosinopaenia and elevated LDH were significantly associated with disease severity in both univariate and multivariate regression models including the above variables. Moreover, eosinophil count and LDH level tended to return to normal range over time in both groups after treatment and severe patients recovered slower than non-severe patients, especially in eosinophil count. CONCLUSIONS: Eosinopaenia and elevated LDH are potential predictors of disease severity in patients with COVID-19 with underlying chronic airway diseases. In addition, they could indicate disease progression and treatment effectiveness.

A Potential circRNA-miRNA-mRNA Regulatory Network in Asthmatic Airway Epithelial Cells Identified by Integrated Analysis of Microarray Datasets.

Background: Asthma is one of the most prevalent chronic respiratory diseases worldwide. Bronchial epithelial cells play a critical role in the pathogenesis of asthma. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges to regulate downstream gene expression. However, the role of epithelial circRNAs in asthma remains to be investigated. This study aims to explore the potential circRNA-miRNA-messenger RNA (mRNA) regulatory network in asthma by integrated analysis of publicly available microarray datasets. Methods: Five mRNA microarray datasets derived from bronchial brushing samples from asthma patients and control subjects were downloaded from the Gene Expression Omnibus (GEO) database. The robust rank aggregation (RRA) method was used to identify robust differentially expressed genes (DEGs) in bronchial epithelial cells between asthma patients and controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to annotate the functions of the DEGs. Protein-protein interaction (PPI) analysis was performed to identify hub genes. Three miRNA databases (Targetscan, miRDB, and miRWalk) were used to predict the miRNAs which potentially target the hub genes. A miRNA microarray dataset derived from bronchial brushings was used to validate the miRNA-mRNA relationships. Finally, a circRNA-miRNA-mRNA network was constructed via the ENCORI database. Results: A total of 127 robust DEGs in bronchial epithelial cells between steroid-naïve asthma patients (n = 272) and healthy controls (n = 165) were identified from five mRNA microarray datasets. Enrichment analyses showed that DEGs were mainly enriched in several biological processes related to asthma, including humoral immune response, salivary secretion, and IL-17 signaling pathway. Nineteen hub genes were identified and were used to construct a potential epithelial circRNA-miRNA-mRNA network. The top 10 competing endogenous RNAs were hsa_circ_0001585, hsa_circ_0078031, hsa_circ_0000552, hsa-miR-30a-3p, hsa-miR-30d-3p, KIT, CD69, ADRA2A, BPIFA1, and GGH. Conclusion: Our study reveals a potential role for epithelial circRNA-miRNA-mRNA network in the pathogenesis of asthma.

Increased epithelial galectin-13 expression associates with eosinophilic airway inflammation in asthma.

BACKGROUND: Airway eosinophilic inflammation is a central feature in asthma which is mainly driven by type 2 response. The expression of galectin-13 was up-regulated in a parasitic infection model which is also characterized by type 2 immune response. We hypothesized that galectin-13 may be involved in airway eosinophilic inflammation in asthma. OBJECTIVE: To unveil the role of galectin-13 in asthma airway inflammation. METHODS: We measured galectin-13 expressions in bronchial brushings, sputum, and plasma of asthma patients (n = 54) and healthy controls (n = 15), and analysed the correlations between galectin-13 expression and airway eosinophilia. We used human bronchial epithelial cell line 16HBE to investigate the possible mechanism by which galectin-13 participates in eosinophilic inflammation. RESULTS: The expression of galectin-13 was markedly increased in subjects with asthma compared to controls. Epithelial galectin-13 mRNA levels in asthmatic subjects were strongly correlated with eosinophilic airway inflammation (the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa and FeNO) and the expression of Th2 signature genes (CLCA1, POSTN and SERPINB2). Inhaled corticosteroid (ICS) treatment reduced plasma galectin-13 levels, and baseline plasma galectin-13 levels reflect the response to ICS treatment. In cultured 16HBE cells, knockdown of galectin-13 suppressed IL-13-stimulated MCP-1 and eotaxin-1 expression by inhibiting the activation of EGFR and ERK. CONCLUSIONS & CLINICAL RELEVANCE: Galectin-13 is a novel marker for airway eosinophilia in asthma, and may contribute to allergic airway eosinophilic inflammation by up-regulating the expression of MCP-1 and eotaxin-1. Plasma galectin-13 levels may be useful for predicting responses to ICS treatment.

Epithelial miR-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma.

The epithelial cell-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) initiate type 2 inflammation in allergic diseases, including asthma. However, the signaling pathway regulating these cytokines expression remains elusive. Since microRNAs are pivotal regulators of gene expression, we profiled microRNA expression in bronchial epithelial brushings from type 2-low and type 2-high asthma patients. miR-206 was the most highly expressed epithelial microRNA in type 2-high asthma relative to type 2-low asthma but was downregulated in both subsets compared with healthy controls. CD39, an ectonucleotidase degrading ATP, was a target of miR-206 and upregulated in asthma. Allergen-induced acute extracellular ATP accumulation led to miR-206 downregulation and CD39 upregulation in human bronchial epithelial cells, forming a feedback loop to eliminate excessive ATP. Airway ATP levels were markedly elevated and strongly correlated with IL-25 and TSLP expression in asthma patients. Intriguingly, airway miR-206 antagonism increased Cd39 expression; reduced ATP accumulation; suppressed IL-25, IL-33, and Tslp expression and group 2 innate lymphoid cell expansion; and alleviated type 2 inflammation in a mouse model of allergic airway inflammation. In contrast, airway miR-206 overexpression had opposite effects. Overall, epithelial miR-206 upregulates airway IL-25 and TSLP expression by targeting the CD39-extracellular ATP axis, which represents a potentially novel therapeutic target in type 2-high asthma.

WeSeer: Visual Analysis for Better Information Cascade Prediction of WeChat Articles.

Social media, such as Facebook and WeChat, empowers millions of users to create, consume, and disseminate online information on an unprecedented scale. The abundant information on social media intensifies the competition of WeChat Public Official Articles (i.e., posts) for gaining user attention due to the zero-sum nature of attention. Therefore, only a small portion of information tends to become extremely popular while the rest remains unnoticed or quickly disappears. Such a typical "long-tail" phenomenon is very common in social media. Thus, recent years have witnessed a growing interest in predicting the future trend in the popularity of social media posts and understanding the factors that influence the popularity of the posts. Nevertheless, existing predictive models either rely on cumbersome feature engineering or sophisticated parameter tuning, which are difficult to understand and improve. In this paper, we study and enhance a point process-based model by incorporating visual reasoning to support communication between the users and the predictive model for a better prediction result. The proposed system supports users to uncover the working mechanism behind the model and improve the prediction accuracy accordingly based on the insights gained. We use realistic WeChat articles to demonstrate the effectiveness of the system and verify the improved model on a large scale of WeChat articles. We also elicit and summarize the feedback from WeChat domain experts.

Highly expressed CCR7 predicts poor prognosis in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NC) is a malignant human tumor with a high incidence that occurs on the top and lateral wall of the nasopharynx. AIMS: To investigate the clinical value of chemokine receptor 7 (CCR7) in locally advanced NC. METHODS: We enrolled 114 patients with locally advanced NC admitted to our hospital in the observation group (OBG) and 100 normal healthy subjects who underwent physical examination in the control group (COG). The serum CCR7 expression levels in each group were measured using enzyme-linked immunosorbent assay and were compared between the groups. RESULTS: None of the 114 patients or their family members were lost during follow-up. Thirty-five patients died within 3 years and 79 survived (survival rate: 69.29%). The serum CCR7 level was higher in the OBG than in the COG (P < 0.05). The receiver operating characteristic (ROC) curve showed that the area under the ROC curve (AUC) was 0.837 for diagnostic value for locally advanced NC and the AUC was 0.759 for predictive value for 3-year mortality. The CCR7 AUC for diagnosis of locally advanced NC was 0.837 and for prediction of mortality was 0.759. Univariate analysis revealed significant differences in smoking history, long-term consumption of pickled food, family history of NC, primary lesion staging, lymph node staging, distant metastasis, clinical pathological staging, and CCR7 between the two groups (P < 0.05). CONCLUSIONS: CCR7 was valuable in the diagnosis of locally advanced NC, and highly expressed CCR7 was predictive of poor prognosis.

Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation.

Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in an animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR) and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN, and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.

GR1-like gene expression in Lycium chinense was regulated by cadmium-induced endogenous jasmonic acids accumulation.

KEY MESSAGE: The G1-like gene from the Lycium chinense was cloned and transferred into N. tabacum. Evidence showed that endogenous JA accumulation was crucial to LcGR gene expression in cadmium-stressed L. chinense. Glutathione reductase (GR) plays a vital role in glutathione-ascorbate metabolism and is a key enzyme in maintaining the redox state in plants. Jasmonic acids (JA) are important hormones regulating protective responses against bacteria and mechanic damage in plants. At present, the relationship between the endogenous JA accumulation, the glutathione (GSH) content and GR gene expression in plants under cadmium (Cd) stress has not been elucidated. This study primarily aims to explore their interconnected relations. First, we isolated the GR1-like gene from Lycium chinense (LcGR). Real-time PCR showed that gene LcGR and allene oxide cyclase (LcAOC) (a JA synthesis gene) expression in L. chinense plants was significantly enhanced by CdCl2 and reduced by CdCl2 cotreatment with 12,13-epoxy-octadecenoic acid (EOA), a JA synthesis inhibitor. Meanwhile, the JA content in plants strongly increased under Cd stress and decreased under Cd + EOA treatment, which was in accordance with expression pattern of LcAOC. The function of gene LcGR was confirmed in vitro with E. coli expression system. The subcellular localization in chloroplasts of LcGR gene was proved in Nicotiana tabacum leaves with transient transfection system of Agrobacterium tumefaciens. Furthermore, the overexpression of gene LcGR in the transgenic tabacum led to great Cd-tolerance and higher GSH accumulation. Overall, the results showed that the endogenous JA accumulation in Cd-stressed plants affects the GR expression which is crucial to the GSH accumulation and GSH-dependent tolerance to cadmium in LcGR transformants.

Association between ORMDL3 polymorphism and susceptibility to asthma: a meta-analysis.

The aim of this study was to determine whether orosomucoid1- like 3 (ORMDL3) single nucleotide polymorphisms rs7216389, rs11650680, rs12603332 are associated with susceptibility to asthma. We performed a meta-analysis by searching PubMed, EMBASE, Elsevier and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. We examined the association between the three SNPs and asthma risk in four genetic models (TT + TC vs. CC, TC vs. CC, TT vs. CC, TT vs. TC + CC). Thirteen published case-control studies involving 6462 cases and 7357 controls were included. Our meta-analysis indicated that rs7216389 was significantly associated with increased asthma risk in overall population. Subgroup analysis by age indicated significant association between the rs7216389 and asthma in children. Moreover, ORMDL3 rs11650680 was significantly associated with decreased asthma risk in dominant model (TT + TC vs. CC), and rs12603332 was significantly associated with decreased asthma risk in 3 models (TT + TC vs. CC, TC vs. CC and TT vs. CC). To Conclude, ORMDL3 rs7216389 polymorphism is associated with susceptibility to asthma. Children with variant T allele (TT or TC) and adults with TT homozygote in rs7216389 are at high risks to suffer from asthma. However, people with T allele in rs11650680 or rs12603332 are protected from asthma.

The association between CD209 gene polymorphisms and pulmonary tuberculosis susceptibility: a meta-analysis.

AIM: Three common polymorphisms in CD209 gene (-336A/G, -871A/G and -139G/A) have been reportedly associated with pulmonary tuberculosis risk. However, the findings from different studies were inconsistent. Therefore, we conducted a comprehensive meta-analysis to determine the association between CD209 gene polymorphisms and pulmonary tuberculosis susceptibility. METHODS: The PubMed, SCI and Elsevier were searched up to April 18, 2015 for studies on the association of CD209 gene polymorphisms and pulmonary tuberculosis. Pooled odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated in a fixed-effects or random-effects model. RESULTS: Twelve case-control studies with 3114 cases and 3088 controls were included. For -871A/G mutation, significant decreased pulmonary tuberculosis risk was observed in allele model (G vs. A: P = 0.009; OR = 0.70, 95% CI = 0.54-0.92), heterozygous model (AG vs. AA: P = 0.009; OR = 0.59, 95% CI = 0.40 to 0.88) and dominant model (AG+GG vs. AA: p =0.01; OR = 0.61, 95% CI = 0.42 to 0.89). For -336A/G polymorphism, no associations were found in all genetic models. In the subgroup analysis by ethnicity, statistical association was observed for Asians in GG vs. AA (P = 0.04; OR = 2.31, 95% CI = 1.05-5.09). No significant association was identified between -139G/A variation and pulmonary tuberculosis risk. CONCLUSIONS: This meta-analysis provides evidences that CD209 gene -871A/G is associated with decreased susceptibility to pulmonary tuberculosis in overall population; -336A/G polymorphism is associated with increased susceptibility of pulmonary tuberculosis in Asians. However, the -139G/A polymorphism is not associated with susceptibility to pulmonary tuberculosis.