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The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-β to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-β precursor to its mature form, TGF-β. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.

Background Coronary artery bypass grafting (CABG) is widely performed across China. Understanding current between-hospital variation is important for further quality improving initiatives. Purpose To assess the between-hospital variation comprehensively on outcomes of isolated CABG, and explore hospital-level characteristics and practice patterns explaining the variation. Methods We used the data of Chinese Cardiac Surgery Registry (2013–2019) to examine the between-hospital variation of outcomes, including in-hospital mortality (or treatment withdrawal) and major complications (mortality, postoperative myocardial infarction, stroke, renal failure, mediastinal infection, and reoperation for bleeding). Multilevel mixed-effect models and propensity score adjusting technique were used to quantify the variability and study hospital-level factors associated with the variation. Risk-standardized mortality rate (RSMR) was used to classify hospital performance. Results Among 60876 patients (62.6 years old, 75.4% male) undergoing isolated CABG in 70 hospitals, the mortality was 2.0% and 5.3% had major complications. After adjusting for patient case-mix, the median hospital RSMR was 2.1% (inter-quartile range [IQR], 1.3%-3.1%), with the median odds ratio (MOR) of 2.1; and 5.7% (IQR, 3.7%-7.5%) for risk-standardized major complications, with the MOR of 1.9. Compared with patients admitted in average-performance hospitals, patients undergoing CABG in worse-performance hospitals had a nearly twofold higher odds of in-hospital mortality (adjusted odds ratio [AOR]=1.92; 95% confidence interval (CI), 1.37–2.69), whereas patients in better-performance hospital had an approximately 60% lower odds (AOR=0.41; 95% CI, 0.30–0.57). Hospital location and average surgeon volume explained 20.2% of the between-hospital variation, where hospital-level perioperative blood transfusion rate and use of secondary prevention medication further contributed to the proportion change variance of 3.3% and 2.3%, respectively. Similar results were obtained for major complications. Conclusion(s) Consistent between-hospital variation of CABG performance exists in China. Improving the clinical practice management and reducing variability may better the overall outcomes. Funding Acknowledgement Type of funding sources: None.

Background Skewed T helper (Th)2 response plays a crucial role in the pathogenesis of allergic diseases. The therapeutic efficacy for allergic diseases is unsatisfactory currently. This study aims to regulate the skewed Th2 response with CARsomes. Methods The CARsome consisted of an epitope of Dermatophagoides farina-1 (Derf1), a segment of the anti-DEC205 antibody, the scFv, and an open reading frame of perforin. This fusion protein binds to DEC205 molecule on the surface of exosomes derived from dendritic cells (DC). The effects of CARsome on inducing antigen (Ag)-specific Th2 cell apoptosis were assessed both in vivo and in vitro. Results Exposure to CARsomes in the culture induced Ag-specific Th2 cell apoptosis. Injection of CARsomes through the vein puncture also induced Ag-specific Th2 cell apoptosis in the lungs of sensitized mice. CARsomes could induce Ag-specific regulatory T cells. Administration of CARsomes efficiently inhibited experimental allergic airway inflammation. Conclusions The CARsomes can inhibit allergic airway inflammation by inducing Ag-specific Th2 cell apoptosis and induce Ag-specific regulatory T cells. The data suggest that CARsomes have the translational potential to be used to treat allergic airway inflammation.

Background: Many studies have demonstrated the efficacy of single-allergen sublingual immunotherapy (SLIT) in polysensitized patients with allergic rhinitis (AR), but less is reported in polysensitized patients with allergic asthma (AS). Method: Data of 133 adult patients with house dust mite (HDM)-induced AS who had been treated for 3 years were collected. These patients were divided into the control group (treated with low to moderate dose of inhaled glucocorticoids and long-acting β2 agonists, n = 37) and the SLIT group (further treated with Dermatophagoides farinae drops, n = 96). The SLIT group contained three subgroups: the single-allergen group (only sensitized to HDM, n = 35), the 1- to 2-allergen group (HDM combined with one to two other allergens, n = 32), and the 3-or-more-allergen group (HDM combined with three or more other allergens, n = 29). The total asthma symptom score (TASS), total asthma medicine score (TAMS), and asthma control test (ACT) were assessed before treatment and at yearly visits. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was assessed before treatment and at the end of SLIT. Results: TASS and ACT scores in the control group were significantly higher than that in the single-allergen group and the 1- to 2-allergen group after 1, 2, and 3 years of SLIT and significantly higher than that in the 3-or-more-allergen group after 3-year SLIT (all p < 0.05). TAMS of the control group was significantly higher than that of the other three groups after 0.5, 1, 2, and 3 years of SLIT (all p < 0.05). FEV1/FVC in the control group was significantly higher than baseline after 3 years of immunotherapy (p < 0.05). Conclusion: Patients sensitized to HDM with/without other allergens showed similar efficacy after 3 years of SLIT. However, the initial response of patients with three or more allergens was slower during immunotherapy process.

Background Heart failure (HF) is a global public health problem, which causes high mortality. Purpose To characterize the pattern of 1-year mortality, including the rate and timing of death, and to identify clinical and non-clinical factors predicting 1-year all-cause mortality after hospitalization for HF. Methods We prospectively enrolled patients who were hospitalized primarily for HF and discharged alive from 52 hospitals across 20 provinces in China between August 2016 and May 2018, and followed them up by face-to-face interview or telephone. Patients' fatal status were ascertained according to investigators' report and national death registration. Cognitive function was measured by Mini-Cog score and health status was measured by Kansas City Cardiomyopathy Questionnaire (KCCQ). We fitted a Cox proportional hazards model accounting for hospital as random effects to identify patient characteristics associated with 1-year all-cause mortality. Results Among 4899 patients, 4882 (97.7%) completed 1-year follow-up. The median (IQR) age was 67 (57, 75) years and 37.5% were women. The main etiology of HF was ischemic heart disease (53.1%), 66.0% of patients had history of HF before the index hospitalization. Among 813 deaths within one year after discharge, 13.4% and 58.4% occurred within one months and six months, respectively. Systolic blood pressure Conclusion In China, one in six patients hospitalized for HF die within 1-year, with the majority occurring during the first 6 months after hospital discharge. Both clinical and non-clinical factors predict 1-year mortality. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The National Key Research and Development Program from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science; the 111 Project from the Ministry of Education of China

Micranthanosides I and II (1–2), two diterpenoid glucosides featuring a new 1,10-secograyanane skeleton, thirteen new diterpenoid glycosides (3–15), and 21 known analogues were obtained from the ethanol extract of the leaves and twigs of Rhododendron micranthum. Micranthanoside XII (12) represent the first example of 3,5-epoxy-4,5-seco-ent-kaurane diterpenoid. The structures of these compounds were determined by spectroscopic data analysis and quantum chemical calculations. To clarify the chemical basis and provide reference for rational use of this medicinal plant, the antinociceptive and the anti-inflammatory activities of the compounds were tested. In the acetic acid-induced writhing test, compounds 17 and 19 showed significant antinociceptive activity at a dose of 3 mg kg−1 and compounds 2, 6 and 32 showed significant antinociceptive activity at a dose of 10 mg kg−1. Toxic reactions such as nausea and convulsion were observed when 17, 19, 29, and 31 at a dose of 10 mg kg−1 or 30 and 33 at a dose of 1 mg kg−1 were administered. The anti-inflammatory activities of the isolated compounds were evaluated by measuring the inhibitory effects of LPS-induced NO production in BV2 cells. At 10 μM, micranthanoside IX (9) and rhodomicranoside F (26) showed moderate anti-inflammatory activities with inhibition rates of 56.31% and 72.43%, respectively.

Background Cardiovascular diseases (CVD) is the leading cause of death in China. Secondary prevention medications can improve the prognosis of CVD, yet little is known about the current use, variation and associated factors of these therapies in China. Purpose The aim of this study was to describe the current use of secondary prevention medications among patients with established CVD in the community setting in China, assess variations across population subgroups, and identify the individual characteristics associated with these therapies. Methods We studied 2.6 million participants aged 35–75 years from all 31 provinces in the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project, a government-funded public health program conducted from 2014 to 2018. Participants self-reported their history of ischemic heart disease (IHD) or ischemic stroke (IS) and medication use in an interview. Among participants with IHD and/or IS, we assessed the reported use of secondary prevention medications (anti-platelet drugs and statins) in the overall population and in 1,530,408 population subgroups, defined by all possible combinations of 16 factors (age, sex, urbanity, geographic region, ethnicity, occupation, annual household income, education, marital status, medical insurance, current smoker, current drinker, history of hypertension, history of diabetes, body mass index and years since diagnosis). Multivariable mixed models with a logit link function and community-specific random intercepts were fitted to assess the associations of demographic, socioeconomic and health behavior factors with the reported use of secondary prevention mediations. Results Among 2,613,035 screened participants, 2.9% (74,830) had history of IHD and/or IS (1.2% for IHD, 2.4% for IS). Overall, the reported use rate either anti-platelet drugs or statins was 21.9% (18.3% anti-platelet drugs, 11.0% statins, and 7.4% both). Among the 1,530,408 population subgroups, the use of secondary prevention medications varied substantially (3.4% to 52.0%). Multivariable analyses found that that younger people, women, those living in rural areas, current smokers, current drinkers, people without hypertension or diabetes, and those with established CVD for more than 2 years were less likely to take anti-platelet drugs or statins (Figure). Forest plot of multivariable mixed model Conclusions The current use of secondary prevention drugs is suboptimal and varies substantially across population subgroups in China. Our study identifies target populations for interventions to improve secondary prevention of CVD. Acknowledgement/Funding This study was supported by the Ministry of Finance of China and National Health Commission of China

Background Recent evidence suggests that preoperative antiplatelet regimen with aspirin can be safely used for patients scheduled for coronary artery bypass grafting (CABG), aiming to maintain graft patency and reduce ischemic complications at an acceptable bleeding risk. However, little is known regarding the safety and efficacy of preoperative low-dose dual antiplatelet therapy with aspirin combined clopidogrel for CABG patients. Objective To investigate the efficacy and safety of preoperative low-dose dual antiplatelet therapy with aspirin combined clopidogrel for patients receiving elective isolated CABG. Methods We retrospectively reviewed data from patients underwent isolated elective CABG in our single institution from January 2013 to March 2017. Dual antiplatelet therapy was determined as aspirin (100 mg daily) five days and clopidogrel (75 mg daily) three days proximity to the surgery. Propensity score matching was used to generate matched groups from patients taken dual antiplatelet therapy and aspirin alone. The Kaplan–Meier method and the log-rank test were applied to create and examine survival curves. Cox proportional hazards regression was employed to explore the differences in early-term outcomes between the two strategies. The primary outcome was in-hospital major adverse cardiac and cerebrovascular events (MACCEs, including all-cause death, nonfatal MI and nonfatal stroke). The secondary outcomes were perioperative bleeding complications (re-exploration for bleeding and blood products transfusion), and MACCEs at six months after surgery. Results From January 2013 to March 2017, 1102 patients received 100 mg aspirin daily five days prior to CABG, and 295 of them combined clopidogrel (75mg daily). Patients on dual antiplatelet therapy with aspirin combined clopidogrel were more often underwent previously stent implantation (14.2% versus 7.7%), and no significant difference regarding other patient baseline characteristics was observed between the two groups. Propensity score matching created 295 well-matched sets (dual antiplatelet therapy versus aspirin alone). Compared with preoperative aspirin alone, dual antiplatelet therapy was associated with more in-hospital major adverse cardiac and cerebrovascular events (Odds Ratio [OR], 2.59; 95% confidence internal [CI], 1.05–6.39; P=0.039), and also higher rates of perioperative blood products transfusion (47.1% versus 34.6%, OR 1.69, 95% CI, 1.21–2.35, P=0.002). After 6 months' follow-up (median 198 days), there were 25 patients (8.5%) with an event in the dual antiplatelet therapy group and 12 patients (4.1%) with an event in the aspirin alone group (Hazard Ratio [HR], 2.12; 95% CI, 1.06–4.22; P=0.033). MACCEs at 6 months after CABG Conclusions For patients receiving elective isolated CABG, preoperative low-dose dual antiplatelet therapy with aspirin combined clopidogrel may result in increased early major adverse cardiac and cerebrovascular events and more perioperative blood transfusions.

Background It has been reported that coronary artery disease (CAD) is characterized by inflammation and non-obstructive CAD (NOCAD) increases the risk of cardiovascular events (CVEs) compared with ones with normal or near-normal coronary arteries (NNCA), even is similar to obstructive CAD (OCAD). We hypothesized that elevated high-sensitivity C-reactive protein (hs-CRP) may be linked to CVEs in those patients with NOCAD. Purpose To investigate the predictive role of hs-CRP in patients with NOCAD. Methods Of 7,746 consecutive patients with angina-like chest pain admissions, 4,662 eligible patients were enrolled who received coronary artery angiography (CAG) and followed up for the CVEs comprising all-cause mortality, myocardial infarction, stroke and late revascularization. According to the results of CAG, the patients were classified as NNCA group (3 mg/L). Proportional hazards models were used to assess the risk of CVEs in all patients enrolled. Results A total of 338 patients (7.3%) experienced CVEs during an average of 13403 person-years follow-up. Patients with NOCAD and OCAD had higher rates of CVEs compared to those with NNCA (p Conclusions Patients with NOCAD had indeed worse outcomes and hs-CRP levels were positively in relation to the CVEs in those with NOCAD, which may help to the risk assessment in ones with NOCAD. Acknowledgement/Funding This study was partly supported by Capital Health Development Fund (201614035) and CAMS Innovation Fund for Medical Sciences (2016-I2M-1-011) awarded

Phytochemical investigation of the roots of Rhododendron molle led to the isolation of 15 new oleanane- and ursane-type triterpenoid compounds (1–15) along with 2 known triterpenoid compounds (16 and 17). The structures of the new compounds were determined by NMR analysis, ESIMS methods and X-ray diffraction. Notably, compound 1 is the first example of a 23-nor-ursane-type triterpenoid with 5/5/6/6/6/6-fused ring system. Compounds 2–5 are 7/6/6/6/6-fused triterpenoids. Compounds 6–9 are 23-nor-2,3-seco 6/6/6/6-fused triterpenoids. Compounds 10 and 11 are 3, 23, 24-trinor-2,4-seco 6/6/6/6-fused triterpenoids. In a membrane potential FLIPR assay, compounds 2, 14–17 (10 μM) induced the activation of GABAA receptors in the presence of GABA (0.2 μM), with increases in activation of 67.9%, 64.2%, 57.9% and 58%, respectively.

The phytochemical study of the ethanol extract of the leaves and twigs of Rhododendron decorum afforded a new ascorbic acid derivative (1), a new ionone analogue (2), a new ursane-type triterpenoid glucoside (3), and four known compounds (4−7). The structures were elucidated by spectroscopic analyses, including HRESIMS, 1D, and 2D NMR. The anti-neuroinflammatory activities of the compounds were evaluated by measuring inhibitory effects of LPS-induced NO production in BV2 cells.

In the study, N-t-butyl-2-benzothiazole sulfenimide (TBSI) was prepared by NS-acetic anhydride method with acetic anhydride as solvent. It was detected with FTIR, XRD, UV-Vis, TG-DTA. Micro-structure and essence disciplinarian of them were disclosed. Chemical bond types into TBSI molecule were revealed with FTIR. TBSI phase composition and structure were revealed with crystallographic data from XRD detecting such as cell parameters and crystal face index. The phase composition and qualitative identification of TBSI structure were completed. The absorption peaks were detected by UV-vis at 228.3, 281.3 and 298.3 nm, respectively caused by n→σ*, π→π*, n→π* electron transition. It could provide basic data with the enterprise of ZBPD product quality inspection. Two kinds of information were detected with TG-DTA as quality change and thermal effect. There were three absorption peaks of 46.5, 188.9, 368. 5 ℃ due to a few residual solvent volatilization in the sample, phase transition peak and decomposition peak. The decomposition temperature of TBSI was very high. It could provided reference with research on rubber vulcanizing properties with TBSI on rubber vulcanizing machine. This study could provide basis experimental data on the enterprises to designate the working standard tracing detection of TBSI industrialized production. Performance index of TBSI was judged. The project of TBSI industry standard could be declared by the enterprises, written a draft standard.

Three new leucothane-type (1–3), two new micrathane-type (4, 5), eight new grayanane-type diterpenoids (6–13), and four known compounds were obtained from the ethanol extract of the leaves and twigs of Rhododendron decorum. The structures were determined based on NMR spectra, quantum chemical calculations, and X-ray crystallography. The antinociceptive activities of compounds 1, 3, 4, 6, 8, 10–13, and 15–17 were evaluated via the acetic acid-induced writhing test. Compounds 1, 8, 11–13, and 15 exhibited significant antinociceptive activities. In particular, 12 and 15 were found to be effective at doses of 0.8 and 0.08 mg/kg, respectively.

The T helper 1 (Th1) polarization plays a critical role in the pathogenesis of a number of inflammatory disorders in the body; the remedies in the correction of polarized Th1 cells are limited. This study aims to investigate the role of T cell immunoglobulin mucin domain molecule 4 (TIM4) in the induction of Th1 cell apoptosis. In this study, polarized Th1 cells were generated from naive Th1 cells from the mouse spleen. Recombinant TIM4 was added to the culture to stimulate the polarized Th1 cells. The apoptosis of Th1 cells was assessed by flow cytometry. The expression of FasL was analyzed by chromatin immunoprecipitation, real time RT-PCR, and Western blotting. The results showed that the polarized Th1 cells expressed high levels of TIM3. After exposure of the polarized Th1 cells to TIM4 in the culture, a complex of TIM3 and TIM4 was detected on the surface of Th1 cells, which induced the Th1 cell apoptosis. The engagement of TIM3 by TIM4 increased p300 phosphorylation in Th1 cells, which further increased the levels of Fas ligand in the cells and induced Th1 cell apoptosis. In conclusion, TIM4 binds TIM3 on the surface of polarized Th1 cells to induce Th1 cell apoptosis, which may contribute to the development of Th2-dominant immune disorders.

Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy.

The initiation mechanism of IgE expression has not been fully understood. Flagellin (FGN) is an important microbial factor in the regulation of immune responses in the intestine. This study tests a hypothesis that FGN plays a crucial role in the isotype switching of IgE in B cells and the initiation of food allergy. In this study, the expression of IgE in B cells was analyzed by real time RT-PCR, Western blotting and chromatin immunoprecipitation. A mouse model was developed to assess the role of Toll like receptor-5 in the development of IgE-mediated allergic reaction in the intestinal mucosa. The results showed that exposure to FGN suppressed the expression of Bcl6 in B cells via increasing the levels of histone deacetylase (HDAC) 7; the latter up regulated the levels of methylated H3K9 and H3K27, down regulated RNA polymerase II and STAT3 (signal transducer and activator of transcription 3) at the Bcl6 promoter locus. Exposure to FGN and IL-4 markedly increased the expression of IgE in B cells via activating p300, H3K4, Pol II and STAT6 at the IgE promoter locus. As compared with the sensitized wild mice, the sensitized TLR5-deficient mice showed no detectable OVA-specific IgE in the serum; mast cells in the intestinal mucosa were not activated, no apparent allergic symptoms were evoked after the specific antigen challenge. In conclusion, FGN facilitates the initiation of food allergy in mice by triggering IgE transcription in B cells in a Th2 polarization environment via activating HDAC7 and suppressing Bcl6 expression.

The hill-climbing has been improved by using the percentage random step and by changing variable values instantly, which is under the condition of an improvement in the objective function having been made by a step forward of a variable in a certain direction, and the improved hill-climbing has been used to solve nonlinear regression problems , and the specific algorithm steps is given, and it has been validated with satisfactory results by using practical examples.

Based on the generalized symmetry group method presented by Lou and Ma [Lou and Ma, Non-Lie symmetry groups of (2 + 1)-dimensional nonlinear systems obtained from a simple direct method, J. Phys. A: Math. Gen. 38 (2005) L129], firstly, both the Lie point groups and the full symmetry group of the nonisospectral BKP equation are obtained, at the same time, a relationship is constructed between the new solutions and the old ones of equation. Secondly, the nonisospectral BKP can be proved to be Painleve integrability by combining the standard WTC approach with the Kruskal’s simplification, some solutions are obtained by using the standard truncated Painleve expansion. Finally, based on the relationship by the generalized symmetry group method and some solutions by using the standard truncated Painleve expansion, some interesting solution are constructed.

SummaryBackground Allergens from dust mites play a critical role in the pathogenesis of airway allergy. The mechanism by which dust mite allergens induce allergic diseases is not fully understood yet. Objective This study tests a hypothesis that the eighth subtypes of Dermatophagoides farina allergen (Derf8) play an important role in the induction of airway allergy. Methods The protein of Derf8 was synthesized via molecular cloning approach. Dendritic cells (DC) were stimulated with Derf8 in the culture, and then, the expression of T cell immunoglobulin mucin domain 4 (TIM4) in dendritic cells (DC) was analysed. The role of Derf8 in the induction of airway allergy was evaluated with a mouse model. Results Exposure to Derf8 markedly induced the TIM4 expression in DCs by modulating the chromatin at the TIM4 promoter locus. Derf8 played a critical role in the expansion of the T helper 2 response in the mouse airway via inducing DCs to produce TIM4. Administration with Derf8-depleted dust mite extracts (DME) inhibited the allergic inflammation and induced regulatory T cells in mice with airway allergy. Conclusion Derf8 plays an important role in the initiation of dust mite allergy. Vaccination with Derf8-deficient DME is more efficient to inhibit the dust mite allergic inflammation than using wild DME.

Lineage-specific genes (LSGs) are defined as genes found in one particular taxonomic group but have no significant sequence similarity with genes from other lineages, which compose about 10%?20% of the total genes in the genome of a focal organism. LSGs were first uncovered in the yeast genome in 1996. The development of the whole genome sequencing leads to the emergence of studies on LSGs as a hot topic in comparative genomics. LSGs have been extensively studied on microbial species, lower marine organisms, plant (such as Arabidopsis thaliana, Oryza sativa, Populus), insects, primate, etc; the biological functions of LSGs are important to clarify the evolution and adaptability of a species. In this review, we summarize the progress of LSGs studies, including LSGs identification, gene characterization, origin and evolution of LSGs, biological function, and expression analysis of LSGs. In addition, we discuss the existing problems and future directions for studies in this area. Our purpose is to provide some unique insights into the researches of LSGs.

The pathogenesis of some chronic inflammation such as inflammatory bowel disease is unclear. Insulin-like growth factor-1 (IGF1) has active immune regulatory capability. This study aims to investigate into the mechanism by which IGF1 modulates the monocyte (Mo) properties to inhibit immune inflammation in the intestine. In this study, the production of IGF1 by intestinal epithelial cells was evaluated by real time RT-PCR and Western blotting. Mos were analyzed by flow cytometry. A mouse colitis model was created with trinitrobenzene sulfonic acid. The results showed that mouse IECs produced IGF1, which could be up regulated by exposure to CpG-ODN (CpG-oligodeoxynueleotides) in the culture. Culture the CpG-ODN-primed IEC cells and Mos or exposure of Mos to IGF1 in the culture induced the Mos to express IL-10. The IGF1-primed Mos showed the immune suppressive effect on inhibiting the immune inflammation in the mouse colon. In conclusion, the IGF1-primed Mos are capable of suppressing immune inflammation in the intestine.

The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigates the regulation of TWIK-related potassium channel-1 (Trek1) in the restitution of intestinal epithelial barrier functions. The human colon epithelial cell line T84 was cultured in monolayers and used to observe epithelial barrier functions in vitro. An intestinal allergy mouse model was created. Cytokine levels were determined by enzyme-linked immunosorbent assay and western blotting. The results showed that Trek1 deficiency induced T84 monolayer barrier disruption. Allergic responses markedly suppressed the expression of Trek1 in the intestinal epithelia via activating the mitogen-activated protein kinase pathways and increasing the expression of histone deacetylase-1. The inhibition of histone deacetylase-1 by sodium butyrate or the administration of a butyrate-producing probiotic (Clostridium butyricum) restored the intestinal epithelial barrier functions and markedly enhanced the effect of antigen-specific immunotherapy. The data suggest that Trek1 is required for the maintenance of intestinal epithelial barrier integrity. Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment.

Specific immunotherapy (SIT) is the only specific remedy for the treatment of allergic diseases currently. B cells are important immune cells in the immunity. The role of B cells in immune regulatory activities has not been fully understood yet. This study aims to elucidate the role of the thrombospondin (TSP)1-producing B cells in the immune regulatory role of SIT. The results showed that after SIT, the frequency of CD35(+) B cells was increased in the intestine of mice with food allergy. The CD35(+) B cells expressed TSP1 after exposure to specific antigens. Co-culture with the TSP1-producing CD35(+) B cells decreased the levels of CD80/CD86 in dendritic cells; the cells convert naïve CD4(+) T cells to regulatory T cells to inhibit allergic inflammation in the intestine.

The expressions of β1,3-N-acetylglucosamonyltransferase-2 and -8 (β3GnT-2, β3GnT-8),—the two main glycosyltransferases responsible for the synthesis of poly-N-acetyllactosamine (polyLacNAc) in glycans, and β3GnT-5 participating in the syntheses of sphingoglycolipids were studied in leukemia cell lines during differentiation using RT-PCR method. β3GnT-2 and β3GnT-8 distribute widely in six myeloid and monocytoid leukemia cell lines with different abundances, while β3GnT-4 was only present in NB4 cells. ATRA (all-trans retinoic acid) and dimethylsulfoxide (DMSO), which induce the differentiation of HL-60 and NB4 (two human acute myeloid leukemia cell lines) to myelocytic lineage, up-regulated these two enzymes with various degrees at 2 and 72 h of treatment. In HL-60 cells treated with ATRA, the increase of β3GnT-8 was more than β3GnT-2, while in NB4 cells treated with DMSO, the increase of β3GnT-2 was more than β3GnT-8. However, when HL-60 and NB4 were differentiated to monocytic lineage induced by phorbol 12-myristate 13-acetate the expressions of β3GnT-2 and β3GnT-8 showed no alterations or the increase of expressions was far less than those in myelocytic differentiation. By means of FITC-labeled tomato lectin affinity staining and flow-cytometry, it was found that the product of β3GnT-2 and -8, polyLacNAc was also increased on the cell surface of HL-60 and NB4 treated with ATRA or DMSO, but unchanged when treated with PMA. These results were in accordance with the up-regulation of the mRNAs of β3GnT-2 and -8. The expression of β3GnT-5, however, was not changed both in myelocytic and monocytic differentiations. The difference in the up-regulation of β3GnT-2 and -8, especially their products may become a useful index to discriminate the myelocytic and monocytic differentiation of leukemia cells.

To investigate the expression changes of protein kinase C (PKC) and nuclear factor kappa B (NF-kappaB) in lung tissue of patients with chronic obstructive pulmonary disease (COPD).The lung tissues obtained from 15 patients (A group) without COPD and 15 patients (B group) with COPD matched with A group in age and sex undergoing pneumonectomy for peripheral lung cancer. The protein and mRNA level of PKCalpha was determined by using Western blot analysis and reverse transcription polymerase chain reaction respectively. NF-kappaB p65 nuclei positive expression was observed by immunohistochemical technique. Electrophoretic mobility shift assay was used to detect the NF-kappaB/DNA binding activity.(1) Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1(%Pre) and partial pressure of oxygen in artery (PaO2) of B group were significantly lower than that of A group (t=7.73-13.96, P0.01, respectively). (2) There was higher level of PKCalpha/GAPDH mRNA and the relative expression of PKCalpha protein in B group than in A group (t=7.64 and 22.27, P0.01, respectively). (3) There were significant increases in NF-kappaB p65 nuclei positive expression of B group than that of A group (t=112.79, P0.01). The NF-kappaB/DNA binding activity of B group was approximately 3.2-fold that of A group (t=104.80, P0.01). (4) There was a significant negative correlation between PaO2 and the nuclei positive expression rate of NF-kappaB p65 in 15 cases of B group (r=-0.7090, P0.05).The expression of PKCalpha, NF-kappaB p65 nuclei positive expression rate and NF-kappaB/DNA binding activity significantly increase in lung tissues of patients with COPD, suggesting that the activation of PKC and NF-kappaB may contribute to the process of COPD in human.

To investigate the effect of protein kinase C (PKC)-nuclear factor-kappa B (NF-kappaB) signal transduction pathway on proliferation and expression of vascular endothelial growth factor (VEGF) in human pulmonary artery smooth muscle cells (HPASMCs).Cultured HPASMCs in normoxia or hypoxia conditions were divided into three groups and stimulated with or without phorbol 12-myristate 13-acetate (PMA) and pyrrolidine dithiocarbamate (PDTC) in vitro. The three groups were the control group, the PMA group and the PMA + PDTC group. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect VEGF mRNA expression, and the expression of VEGF protein and the inhibitor protein IkappaBalpha were observed by Western blot, while the location and expression of NF-kappaB p65 were observed by immunocytochemical staining, and cell cycle phases were analyzed by flow cytometry.(1) As for the positive rate of nucleolar staining for NF-kappaB p65, the relative expression of IkappaBalpha protein, and the percentage of G(2)/M phases of cell cycle, there were significant differences between the PMA group and the control group or PMA + PDTC group, both in normoxia and hypoxia conditions (P0.05, respectively), and there was also a significant difference between the normoxia and hypoxia PMA groups (P0.05). (2) There were no significant differences in VEGF mRNA and protein expression among the three groups (P0.05, respectively) in normoxia, but the expression was higher in hypoxia PMA group than in hypoxia control and hypoxia PMA + PDTC or normoxia PMA group (P0.05, respectively). (3) There was a positive correlation between the positive rate of nucleolar staining for NF-kappaB p65, the relative expression of VEGF protein and the percentage of G(2)/M phases of cell cycle in hypoxia PMA group (r = 0.587 - 0.710, P0.05, respectively).There is a signal transduction pathway of PKC-NF-kappaB in HPASMCs. The activity of PKC can be enhanced in hypoxia, concomitant NF-kappaB activation or VEGF overexpression to be involved in the proliferation. These results suggest that the activation of NF-kappaB can be considered as a downstream of PKC signal transduction pathway, and the activation of PKC-NF-kappaB signal transduction pathway and VEGF overexpression may contribute to the process of hypoxic pulmonary hypertension.