A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium.

The Drosophila systemic immune response against many Gram-positive bacteria and fungi is mediated by the Toll pathway. How Toll-regulated effectors actually fulfill this role remains poorly understood as the known Toll-regulated antimicrobial peptide (AMP) genes are active only against filamentous fungi and not against Gram-positive bacteria or yeasts. Besides AMPs, two families of peptides secreted in response to infectious stimuli that activate the Toll pathway have been identified, namely Bomanins and peptides derived from a polyprotein precursor known as Baramicin A (BaraA). Unexpectedly, the deletion of a cluster of 10 Bomanins phenocopies the Toll mutant phenotype of susceptibility to infections. Here, we demonstrate that BaraA is required specifically in the host defense against Enterococcus faecalis and against the entomopathogenic fungus Metarhizium robertsii, albeit the fungal burden is not altered in BaraA mutants. BaraA protects the fly from the action of distinct toxins secreted by these Gram-positive and fungal pathogens, respectively, Enterocin V and Destruxin A. The injection of Destruxin A leads to the rapid paralysis of flies, whether wild type (WT) or mutant. However, a larger fraction of wild-type than BaraA flies recovers from paralysis within 5 to 10 h. BaraAs' function in protecting the host from the deleterious action of Destruxin is required in glial cells, highlighting a resilience role for the Toll pathway in the nervous system against microbial virulence factors. Thus, in complement to the current paradigm, innate immunity can cope effectively with the effects of toxins secreted by pathogens through the secretion of dedicated peptides, independently of xenobiotics detoxification pathways.

RAB11A aggravates PDGF-BB-stimulated proliferation, migration, and inflammation of airway smooth muscle cells via affecting the NF-κB and PI3K/AKT pathways.

BACKGROUND: Pediatric asthma is an usual disease and a kind of fearful health threat for children. Airway smooth muscle cells (ASMCs) with increased cell proliferation and migration abilities serve as important features in the progression of asthma. RAB11A has been shown to aggravate cancer progression and is closely associated with inflammation. Gene analysis discovered that RAB11A exhibited higher expression in asthmatic patients. However, the detailed regulatory function of RAB11A in asthma still needs further investigation. METHOD: The mRNA and protein expressions of genes were examined through RT-qPCR and western blot. Cell proliferation was examined through MTT and BrdU assays. Cell apoptosis was tested through flow cytometry. The cell migration ability was detected through wound healing and transwell assays. The levels of TNF-α, IL-1ß, IL-8, and IL-6 were measured through ELISA. RESULT: In this study, the mRNA and protein expressions of RAB11A were increased with PDGF-BB treatment in a dose-dependent manner. Additionally, the silencing of RAB11A suppressed the proliferation ability of PDGF-BB-mediated ASMCs. Moreover, it was uncovered that the knockdown of RAB11A inhibited the migration ability of PDGF-BB-stimulated ASMCs. Besides, suppression of RAB11A relieved the inflammatory response in PDGF-BB-stimulated ASMCs. Lastly, inhibition of RAB11A retarded the NF-κB and PI3K/AKT pathways. CONCLUSION: Our results revealed that RAB11A aggravated PDGF-BB-stimulated proliferation, migration, and inflammation of ASMCs through modulating NF-κB and PI3K/AKT signaling pathways. This finding implied that the RAB11A may be deemed as a novel and prospective biomarker for asthma treatment.

Study on the university students' satisfaction of the wisdom tree massive open online course platform based on parameter optimization intelligent algorithm.

INTRODUCTION: Curriculum learning through the wisdom tree massive open online course platform not only gets rid of the limitations of specialty, school and region, eliminates the limitations of time and space in traditional teaching, but also effectively solves the problem of educational equity. OBJECTIVES: This paper proposes an intelligent algorithm combining decision tree, support vector machine, and simulated annealing to obtain the best classification accuracy and decision rules for university students' satisfaction with the wisdom tree massive open online course platform. METHODS: This study takes the university students in Fuzhou city information management department as the survey object, and adopts the electronic questionnaire survey method. A total of 1136 formal questionnaires were responded, and 1028 valid questionnaires were obtained after data cleaning and deleting invalid questionnaires (the effective rate was 90.49%). In this paper, the reliability and validity of the questionnaire were tested by IBM SPSS-20.0 software, and six explanatory variables including function, achievement, exercise, quality, richness, and interaction were obtained by principal component analysis. Then, the questionnaire data is converted to CSV (comma separated values) format for analysis. This paper proposes an intelligent algorithm combining decision tree, support vector machine, and simulated annealing to obtain the best classification accuracy and decision rules for university students' satisfaction with the wisdom tree massive open online course platform. In this paper, the proposed algorithm is compared with decision tree, random forest, k-nearest neighbor, and support vector machine to verify its performance. RESULTS: The experimental results show that training set classification accuracy of decision tree, random forest, k-nearest neighbor, only support vector machine and the proposed algorithm (simulated annealing + support vector machine) are 92.21%, 96.10%, 95.67%, 97.29%, and 99.58%, respectively. CONCLUSION: The proposed algorithm simulated annealing + support vector machine does increase the classification accuracy. At the same time, the 11 decision rules generated by simulated annealing + decision tree can provide useful information for decision makers.

[Application of standardized venous thromboembolism prevention program in burn patients].

OBJECTIVE: To develop a standardized venous thromboembolism (VTE) prevention program for burn patients and verify its safety and effectiveness by comparing with traditional thrombus prophylaxis. METHODS: All burn patients admitted and met selection criteria betweem April 2017 and September 2018 were included. Patients between January 2018 and September 2018 were included as the interventional group to implement standardized VTE prevention programs, while patients between April 2017 and December 2017 were included as the control group and traditional active and passive exercises were used to prevent VTE. There was no significant difference in the age, gender, ethnic group, marriage, education, occupation, type and site of the injury, burn area, operation time, and hospital stay between the two groups ( P>0.05), which was comparable. The incidence of VTE, number of cases of tissue or organ hemorrhage, survival rate of skin grafting, and time of wound healing were compared. RESULTS: The incidence of VTE was obviously lower in the interventional group (1.56%, 1/64) than in the control group (10.17%, 6/59) ( χ 2=-2.05, P=0.04). No bleeding occurred in any tissue or organ in the two groups. The survival rate of skin grafting and the time of wound healing were 89.06% (57/64) and (11.78±3.08) days respectively in the interventional group and 91.53% (54/59) and (11.66±2.30) days respectively in the control group; and the differences between the two groups were not statistically significant ( χ 2=0.21, P=0.65; t=-0.22, P=0.83). CONCLUSION: The standardized VTE prevention program can effectively prevent the occurrence of VTE, and its safety is relatively high.

Gold nanorods-based thermosensitive hydrogel produces selective long-lasting regional anesthesia triggered by photothermal activation of Transient Receptor Potential Vanilloid Type-1 channels.

Long-lasting regional anesthesia and selective sensory block are useful in post-operative analgesia and treatment of pathological pain. Previous studies have demonstrated that activation of TRPV1 (Transient Receptor Potential Vanilloid Type-1) channels facilitated the potency of QX-314 for selective long-lasting regional anesthesia in vivo. Hydrogel is a solid jelly-like material covering a wide range of properties from soft and weak to hard and tough. Gold nanorods are nanoparticles, which can be used for hyperthermia by exposure to near-infrared radiation. We fabricated a gold nanorods and QX-314 containing hydrogel. The molecular weight of hydrogel was adjusted to achieve a targeted phase transition temperature. Gold nanorods with a desired photothermal conversion efficacy and QX-314 were mixed with hydrogel to produce a gold nanorods-QX-314/hydrogel nanocomposite. A rat model of sciatic nerve block was applied to evaluate the regional anesthetic effect of the gold nanorods-QX-314/hydrogel nanocomposite. Upon exposure to near-infrared irradiation, the gold nanorods-QX-314/hydrogel nanocomposite activated TRPV1 channels through photothermal conversion and release of QX-314 at the same time. The gold nanorods and QX-314 loaded hydrogel exhibited a long-lasting regional anesthetic effect with selective sensory function block. Sensory block duration of the nanocomposite was significantly longer than of 1% lidocaine (90.0 ±â€¯12.2 vs. 37.5 ±â€¯12.5 min, P < 0.01). Motor block by the nanocomposite was observed for only 40% of rats with significantly shorter duration than its sensory block (42.5 ±â€¯17.1 vs. 90.0 ±â€¯12.2 min, P < 0.01). The gold nanorods-QX-314/hydrogel nanocomposite can produce a selective long-lasing regional anesthetic effect in a rat model of sciatic nerve block.

Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced airway asthma and ß-lactoglobulin-induced intestinal food allergy mouse models.

AIM: To determine whether oral administration of Bifidobacterium infantis CGMCC313-2 (B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model. METHODS: Ovalbumin (OVA)-induced allergic asthma and ß-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin (HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVA-specific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid (BALF) were also assessed. In the food allergy mouse model, the levels of total IgE and cytokines in serum were measured. RESULTS: Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total IgE in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4 (IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed. CONCLUSION: B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation.

Oral administration of Clostridium butyricum CGMCC0313-1 inhibits ß-lactoglobulin-induced intestinal anaphylaxis in a mouse model of food allergy.

BACKGROUND: Probiotic bacteria can induce immune regulation or immune tolerance in patients with allergic diseases, but the underlying mechanisms are still unclear. There has been a growing interest in the use of beneficial bacteria for allergic diseases recently. This study aimed at exploring whether Clostridium butyricum CGMCC0313-1 (C. butyricum) can reduce ß-lactoglobulin(BLG)-induced intestinal anaphylaxis in a murine model of food allergy. METHODS: The preventive and therapeutic effects of oral C. butyricum on anaphylactic symptoms induced via BLG in food allergy mice were investigated. Intestinal anaphylaxis, T helper (Th)-specific cytokines and transcription factors, secretory IgA (sIgA), CD4+ CD25+ Foxp3Treg cell and histopathological alterations were examined. RESULTS: Clostridium butyricum significantly ameliorated intestinal anaphylaxis symptoms in the food allergy mice. sIgA and CD4+ CD25+ Foxp3Treg cell were increased by oral C. butyricum. It also reversed the imbalance of Th1/Th2 andTh17/Treg. CONCLUSIONS: Clostridium butyricum reduces BLG-induced intestinal anaphylaxis in mice and might be an additional or supplementary therapy for food allergy.

Loop-mediated isothermal amplification of Neisseria gonorrhoeae porA pseudogene: a rapid and reliable method to detect gonorrhea.

BACKGROUND AND OBJECTIVE: Gonorrhea is a sexually transmitted disease caused by the bacterium Neisseria gonorrhoeae. Rapid detection is crucial for effective prevention and treatment. This study developed and tested a low-cost effective method for detecting N. gonorrhoeae, especially in developing countries. METHODS: DNA from a N. gonorrhoeae standard strain, as well as from 26 genital secretion samples of gonorrhea patients, were isolated and used for loop-mediated isothermal amplification (LAMP) assay, which was conducted using either an automatic real-time PCR analyzer or a water bath. The amplified porA pseudogene sequence was compared with the NCBI database and the LAMP results were compared with that of the traditional culture method for its sensitivity and specificity. RESULTS: LAMP was able to detect Neisseria DNA at a concentration as low as 1 pg/µL (1 × 103 CFU/mL cells). The LAMP assay results obtained using an automatic real-time PCR analyzer was similar to that of the water bath. Relative to traditional culture, the sensitivity and specificity of the LAMP assay were 94.7 and 85.7%, respectively. CONCLUSION: LAMP was sensitive and reliable for detecting the porA gene of N. gonorrhoeae. It could be used as a rapid, low cost, and effective method for detecting N. gonorrhoeae.

Promoting roles of the secreted frizzled-related protein 2 as a Wnt agonist in lung cancer cells.

The secreted frizzled-related protein 2 (SFRP2) plays a pivotal role in the Wnt pathway, however, it functions as an agonist or an antagonist is still controversial. We profiled SFRP2 expression in several lung cancer cell lines, and found that A549 and 95-D exhibited the lowest and the highest level of SFRP2, respectively. Then we employed the SFRP2-overexpressing plasmid and siRNA to transfect A549 and 95-D cells, respectively. Through MTT assays, we found that SFRP2 knockdown inhibited cell proliferation, and halted the 95-D cells in G1 phase of the cell cycle by downregulation of CCND1 and CDK4, indicating that SFRP2 has the ability of promoting lung cancer cell proliferation. We further checked the cell properties of migration and invasion, using wound scratch assay and Transwell assays. The data showed decreased migrated and invasive 95-D cells after SFRP2 knockdown, and the observations were the opposite in the overexpressing model, implying that SFRP2 promoted lung cancer cell invasion. Moreover, the canonical Wnt pathway was also studied through detection of ß-catenin by western blotting. In the SFRP2 overexpressing model, A549 cells presented stronger expression of ß-catenin compared with controls, while it was the opposite in 95-D cells. These results suggested that SFRP2 serves as a Wnt agonist in lung cancer cells. Together, the findings of this study implied that SFRP2 is not only an agonist of Wnt pathway, but also a cancer promoting protein for lung cancer, indicating SFRP2 as a promising therapeutic target for lung cancer treatment.