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Objective: To observe the effect of Haemophilus influenzae colonizing in lower respiratory tract on airway inflammation and immune imbalance in asthmatic mice, and to study the signaling pathway. Methods: Thirty-two C57BL/6 wild type (WT) and 32 TLR4 gene knockout (TLR4-/-) mice were used. The C57BL/6 mice were randomly divided into control group (NC), asthma group (AC), inoculation group (NS) and asthma inoculation group (AS), and there were 8 mice in each group. Thirty-two TLR4-/- mice were grouped same as above. Mice in AC and AS group were sensitized and stimulated by ovalbumin (OVA) to make chronice asthma model. The Hemophilus influenzae AGAR bead was infused into the airway to prepare the airway colonization model. The levels of IL-17 and IL-10 in serum were measured by ELISA. Th17, Treg and TLR4+ cells in spleen nonocytes were isolated and detected by flow cytometry, and the association analysis among them was performed. Results: In C57BL/6 wild type mice, compared with AC, NS and NC group, IL-17, IL-17/IL-10, Th17 and TLR4+ cell increased, and IL-10 and Treg decreased significantly in AS group, which indicated Haemophilus influenza colonization worsen airway inflammation and led to immune imbalance. Compared with AS group of C57BL/6, IL-17, IL-17/IL-10, Th17, Th17/Treg, TLR4+ cells were decreased, and IL-10 and Treg increased in AS Group of TLR4-/mice, which implicated Haemophilus influenza colonization in lower airway might play effect through TLR4-/- signaling pathway. Correlation analysis showed that ratio of CD4+T lymphocyte with TLR4 expression was positively correlated with Th17 ratio(r=0.912, 0.723, P

In order to obtain the optimal vibration response of a seven-axle elevated platform vehicle with hydro-pneumatic suspension（HPS）, a hybrid coupling scheme of parallel connection ＆ contralateral cross-linked for HPS was designed. The dynamic model with 20 degrees of freedom which can comprehensively reflect vehicle coupling vibration including vertical-lateral-longitudinal-transverse was established. The vibration response characteristics of the vehicle and the influence of key parameters were analyzed by joint simulation. A single objective function contains two evaluation indices of vehicle ride comfort and stability was established through analytic hierarchy process（AHP） and range transformation standardization. The parameters optimization calculation of HPS was carried out. The model reference adaptive control, based on the principle of global vibration, applying Lyapunov design adaptive law, was carried on the HPS. The simulation results show that the evaluation index of vehicle vibration response is significantly improved after parameter optimization and superposition adaptive control.

Objective To explore the clinical feasibility of real-time assessment for degree of pain after surgical dental implant placement, and to analyze the related influencing factors of postoperative pain. Methods A total of 233 patients undergoing dental implant surgery in the prosthodontics department from November 2018 to August 2019 were selected by convenient sampling in this study. The postoperative pain was evaluated in real time based on phone follow-up. All the data were collected and analyzed by SPSS 23.0 statistics. The postoperative pain was described statistically, and the predictor variables were tested by Spearman correlation analysis and multiple linear regression analysis. Results Finally, 228 patients were included in the study, and the response rate was 97.9%. Pain intensity was mild for the most patients and the peak of it occurred at the 4th and 6th hour after surgery. Spearman correlation analysis and multiple linear regression analysis indicated that the influencing factors associated with the degree of postoperative pain included premedication with painkiller (P=0.000, P=0.004), the scores of pain sensitivity questionnaire (PSQ-total) (P=0.016, P=0.001) and operation time (P=0.046, P=0.028). Conclusion Our real-time assessment is feasible, and is worthy of clinical promotion. For the patients with high pain sensitivity and longer operation time, painkillers should be recommended to relieve the pain.

Since the 2008 financial crisis, the US has continually imposed unconventional monetary policies, resulting in spillover effects on emerging economies led by the BRICS countries. This paper uses a dynamic panel model to make some analysis from the aspects of economic openness, financial stability, financial openness, banking system and exchange rate system of the BRICS countries, and the results show that there is heterogeneity in the spillover effects of US unconventional monetary policy on different countries, as reflected in the fact that if a country has a higher level of economic openness, poorer financial stability, higher bank loan-to-deposit ratios and lower bank capital-to-asset ratios, it will be more strongly affected by US unconventional monetary policy. Further research shows that BRICS countries are most affected by unconventional monetary policy when their M2 growth rates are significantly different from the US and their exchange rates are wildly fluctuating, at the same time, the effects of economic openness and banking system conditions will no longer be significant. [ABSTRACT FROM AUTHOR]

This paper selects policy texts on collaborative business environment construction issued by cities in Chengdu-Chongqing Economic Circle from 2011 to November 2021, and adopts social network analysis as the method to construct collaborative network of business environment construction in Chengdu-Chongqing region. This paper analyzes the evolution trend of the collaborative network of business environment construction in Chengdu-Chongqing Economic Circle at different stages and the main network structure characteristics at present stage. The results show that the overall network density of the collaborative network of business environment construction in Chengdu-Chongqing Economic Circle is constantly improving, and the cooperation of business environment among cities is constantly intensifying. The collaborative network structure of business environment construction in Chengdu-Chongqing Economic Circle has gradually changed from two-center structure to two-center plus multi-regional structure. In the collaborative network of business environment construction in Chengdu-Chongqing Economic Circle, cooperation among cities is unbalanced in extend and degrees. [ABSTRACT FROM AUTHOR]

The HPS system of seven axle platform fire truck was divided into four parts by the center plane of rolling and pitching. After parallel connection of inner suspension cylinders for each part, the four coupling schemes were designed as follows:four part independent, contralateral rod cavity connection, contralateral cross connection and diagonal cross connection. The mathematical model and AMESim simulation model for each HPS were established. The dynamometer characteristics and stiffness characteristics of vertical, rolling, pitching and torsional were analyzed. The body vibration responses of vehicles with these four kinds of coupled HPS were studied under driving, braking and steering conditions on a multi-axle coupled road simulation test rig. The test results are almost the same with theoretical results. Comparison analyses show that the HPS coupling scheme has less effect on vehicle vertical vibration but greater effect on vehicle attitude stability. The scheme of contralateral cross connection is most suitable for seven axle high platform fire trucks with high centroid position and low rollover threshold. [ABSTRACT FROM AUTHOR]

The adoptive immunotherapy mediated by tumor-infiltrating lymphocytes (TILs) has shown definite efficacy against various solid tumors. However, the inefficiency of the conventional method based on in vitro expansion of TILs fails to achieve the cell count and high tumor-killing activity required for therapeutic purposes. This study investigated the effect of 3D tumor spheroids on the activation and expansion of TILs in vitro , aiming to provide a novel approach for the expansion of TILs. We procured TILs and primary tumor cells from surgical samples of lung cancer patients and then compared the impacts of lung cancer cell line NCI-H1975 and primary lung cancer cells cultured under 2D and 3D conditions on the activation, expansion, and anti-tumor activity of TILs. Furthermore, we added the programmed cell death protein 1 (PD-1) antibody into the co-culture of primary tumor cells and TILs within a 3D environment to assess the effects of the antibody on TILs. The results showed that compared with 2D cultured tumor cells, the 3D cultured H1975 cells significantly enhanced the expansion of TILs, increasing the proportion of CD3 + /CD8 + cells in TILs to 61.6%. The 3D primary tumor model also enhanced the proportion of CD3 + /CD8 + cells in TILs (45.5%, 54.4%), induced apoptosis of tumor epithelial cells and decreased the overall tumor cells survival rate (16.7%) after co-culture. PD-1 antibodies further improved the in vitro expansion capacity of TILs mediated by 3D tumor spheroids, resulting in the proportions of 50.9% and 57.0% for CD3 + /CD8 + cells and enhancing the antitumor activity significantly (reducing the overall tumor survival rate to 9.36%). In summary, the use of 3D tumor spheroids significantly promoted the expansion and improved the anti-tumor effect of TILs, and the use of the PD-1 antibody further promoted the expansion and tumor-killing effect of TILs.

Objective: To synthesize the derivatives of sinomenine, 4-palmitoyl-sinomenine, and explore its therapeutic effect on lipopolysaccharide (LPS)-induced endotoxemia., Methods: A highly efficient synthesis of sinomenine derivatives called 4-palmitoyl-sinomenine was made with a molecule of palmitic acid substitutions at C-16 position of ring A. One hour before endotoxemia induction by i.p. injection of 10 mg/kg LPS, high-dose treatment mice (n=5/group) received an i.p. injection of 5 mg/kg sinomenine or 4-palmitoyl-sinomenine while the low-dose treatment mice (n=5/group) received 2.5 mg/kg sinomenine or 4-palmitoyl-sinomenine. Untreated group and normal control group received normal saline. And their survival was monitored hourly for 24 hours. Examination of cytotoxicity of 4-palmitoyl-sinomenine on RAW264.7 cells was conducted at a concentration range of 1 to 125 μmol/L using MTT assay. RAW264.7 cells were exposed to 4-palmitoyl-sinomenine (0, 1, 2, 5, 10 μmol/L) for 24 hours, and then treated with LPS (1 μg/mL) for 6 hours. Then RAW264.7 cells were collected and the mRNA level of IL-6 was detected by real-time quantitative PCR(qRT-PCR)., Results: Sinomenine derivatives were successfully synthesized to get 4-palmitoyl-sinomenine. The survival percentage of 4-palmitoyl-sinomenine treatment groups was higher than that of sinomenine treatment groups at the same treatment concentration. The 4-palmitoyl-sinomenine inhibited RAW264.7 cell proliferation and IL-6 gene transcription., Conclusion: The 4-palmitoyl-sinomenine has an anti-inflammation probably through inhibiting the proliferation of RAW264.7 cells and decreasing the inflammatory gene expression and inflammatory cytokine release.

Objective: To study the effect of Pa-pex 11 gene on penicillin production in Pencillium aurantiogriseum., Method: Based on the conserved domain of pex 11 from Penicillium chrysogenum, we designed primers pex01 and pex02 to amplify Pa-pex 11 gene from P. aurantiogriseum. The complete Pa-pex 11 gene was cloned via thermal asymmetric interlaced PCR (Tail-PCR). In order to obtain tranformants with additional Pa-pex 11 gene copy, ATMT (Agrobacterium tumefaciens mediated transformation) was used to transform P. aurantiogriseum. The copy number of Pa-pex 11 was measured by quantitative PCR. Penicillin production of the transformant was analyzed by bioassays and the microbodies were observed by transmission electron microscope (TEM)., Results: ATMT was successfully applied in P. aurantiogriseum. Increasing the copy number of Pa-pex 11 gene resulted in a 1.7-fold increase of pencillin production, and the electron microscope graph showed that the number of microbodies increased obviously., Conclusion: Our results suggest that increasing the copy number of Pa-pex 11 can increase the number of microbodies, and stimulate the penicillin production.

Objective: To isolate large genomic DNA fragments from Monascus ruber for the construction of cosmid libraries., Methods: Modified phenol-chloroform method was used to isolate genomic DNA. The isolated genomic DNA was digested by Sau3AI to 40kb fragments on average. Then, the fragments were packaged by Stratagene' s Gigapack III XL packaging extract. A pair of degenerate primers were used to amplify a fragment of PKS (polyketide synthase) gene from this cosmid library., Results: The average size of genomic DNA isolated by this method was larger than 48 kb, with a concentration of 5 microg/microl. The constructed cosmid libraries had 10 folders coverage of the Monascus spp. genome. A cosmid containing the homologue of PKS gene was obtained by PCR screening., Conclusion: This modified method of isolating large fragments genomic DNA of Monascus ruber was efficient and feasible.