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Hemorrhagic shock (HS) is defined as a reduction in tissue oxygenation and organ dysfunction due to severe blood loss. Lung injury is a frequent complication of HS. Baicalin, isolated from Radix Scutellariae, has been reported to profile the antitumor, anti-oxidative, anti-inflammatory, and antibacterial roles in various pathological processes. Nevertheless, the effects of baicalin on HS-induced lung injury are unclear. This study aims to examine the therapeutic effects of baicalin on lung injury. We first established the lung injury rat models by withdrawing blood in the femoral artery followed by resuscitation. A pathological analysis showed that HS-administrated rats presented severe capillary leakage and pulmonary edema, while baicalin therapy alleviated the symptoms. Baicalin therapy reduced the number of macrophages and neutrophils in bronchoalveolar lavage fluid and decreased the expression and activity of myeloperoxidase (neutrophile infiltration marker) in the lung tissues of HS rats, indicating that baicalin alleviated HS-induced infiltration of inflammatory cells. The secretion of inflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, IL-18, and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]), as well as the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome, were inhibited by baicalin administration. Furthermore, we found that the NF-[Formula: see text]B pathway, a canonical pro-inflammatory pathway, was also blocked after treatment with baicalin in HS-evoked rats, as indicated by the decreased expression of p65 and p65 phosphorylation in the lung tissues. In summary, we infer that baicalin may exert a protective role in HS-induced lung injury by suppressing the activation of NLRP3 inflammasome via the NF-[Formula: see text]B pathway.

Objective This study aimed to investigate the linkage of long non-coding RNA (lncRNA) expression profile with etanercept response in rheumatoid arthritis (RA) patients. Methods Peripheral blood mononuclear cell (PBMC) samples were collected from 80 RA patients prior to etanercept treatment. Samples from eight responders and eight non-responders at week 24 (W24) were proposed to RNA-sequencing, then 10 candidate lncRNAs were sorted and their PBMC expressions were validated by reverse transcription quantitative chain reaction (RT-qPCR) in 80 RA patients. Subsequently, clinical response by lncRNA (CRLnc) prediction model was established. Results RNA-sequencing identified 254 up-regulated and 265 down-regulated lncRNAs in W24 responders compared with non-responders, which were enriched in immune or joint related pathways such as B-cell receptor signaling, osteoclast differentiation and T-cell receptor signaling pathways, etc. By reverse transcription quantitative chain reaction (RT-qPCR) validation: Two lncRNAs were correlated with W4 response, three lncRNAs were correlated with W12 response, seven lncRNAs were correlated with W24 response. Subsequently, to construct and validate CRLnc prediction model, 80 RA patients were randomly divided into test set (n = 40) and validation set (n = 40). In the test set, lncRNA RP3-466P17.2 (OR = 9.743, P = .028), RP11-20D14.6 (OR = 10.935, P = .007), RP11-844P9.2 (OR = 0.075, P = .022), and TAS2R64P (OR = 0.044, P = .016) independently related to W24 etanercept response; then CRLnc prediction model integrating these four lncRNAs presented a good value in predicting W24 etanercept response (Area Under Curve (AUC): 0.956, 95%CI: 0.896–1.000). However, in the validation set, the CRLnc prediction model only exhibited a certain value in predicting W24 etanercept response (AUC: 0.753, 95%CI: 0.536–0.969). Conclusions CRLnc prediction model is potentially a useful tool to instruct etanercept treatment in RA patients.

This study aimed to investigate the effect of microRNA 146a (miR-146a) overexpressed bone marrow mesenchymal stem cells (BMMSCs) exosomes on spinal cord injury (SCI) recovery.Rat BMMSCs were isolated and transfected with miR-146a mimic (miR-mimic) and control mimic (NC-mimic), after which their exosomes were isolated. Afterward, SCI rat models were constructed, then treated with phosphate buffer saline (PBS), NC BMMSCs exosomes (separated from the culture medium of BMMSCs with NC-mimic), and miR-146a overexpressed BMMSCs exosomes (isolated from the culture medium of BMMSCs with miR-mimic), respectively; additionally, rats underwent sham surgery were treated with PBS as controls.MiR-146a was upregulated in BMMSCs, and BMMSCs derived exosomes post miR-mimic transfection. Then in SCI rats, BMMSCs exosomes elevated the Basso, Beattie, and Bresnahan (BBB) score and reduced hematoxylineosin-reflected spinal cord tissue injury. In addition, BMMSCs exosomes did not affect TUNEL positive cells rate while increased NeuN(+) cells/field in spinal cord tissue from SCI rats. As for inflammation, BMMSCs exosomes repressed pro-inflammatory cytokine expressions, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, in spinal cord tissue from SCI rats. Furthermore, miR-146a overexpressed BMMSCs exosomes presented with notably better effects regarding elevating BBB score in SCI rats and reducing tissue injury, neuron apoptosis, and inflammation while enhancing neuron viability in spinal cord tissue from SCI rats.MiR-146a overexpressed BMMSCs exosomes enhance locomotor capacity and neuron viability while reducing neuron apoptosis and spinal cord tissue inflammation in SCI rats.

Mechanical vibrations have been an important sustainable energy source, and piezoelectric cantilevers operating at the resonant frequency are regarded as one of the effective mechanisms for converting vibration energy to electricity. This paper focuses on model and experimental investigations of multiple attached masses on tuning a piezoelectric cantilever resonant frequency. A discrete model is developed to estimate the resonant frequencies’ change of a cantilever caused by multiple masses’ distribution on it. A mechanism consisted of a piezoelectric cantilever with a 0.3 g and a 0.6 g movable mass along it, respectively, is used to verify the accuracy of the proposed model experimentally. And another mechanism including a piezoelectric cantilever with two 0.3 g attached masses on it is also measured in the designed experiment to verify the discrete model. Meanwhile, the results from the second mechanism were compared with the results from the first one in which the single attached mass is 0.6 g. Two mechanisms have wildly different frequency bandwidths and sensitivities although the total weight of attached masses is the same, 0.6 g. The model and experimental results showed that frequency bandwidth and sensitivity of a piezoelectric cantilever beam can be adjusted effectively by changing the weight, location, and quantity of attached masses.

This study investigated whether long noncoding RNA interfering EIF3J antisense RNA1 (EIF3JAS1) could affect lung cancer A549 cells as well as the role of microRNA-330-5p (miR-330-5p) during this process. To this end, quantitative real-time polymerase chain reaction was used to measure EIF3J-AS1 and miR-330-5p expression in 39 lung cancer cases. Small interfering RNA targeting EIF3J-AS1 (si-EIF3J-AS1), as well as the miR-330-5p inhibitor, was transfected into lung cancer A549 cells. The outcomes of cell proliferation, clone formation, migration, invasion, and E- and N-cadherin expression were analyzed using CCK-8 kit, clone formation experiment, Transwell method, and Western blot. The targeted binding between EIF3J-AS1 and miR-330-5p was explored using the luciferase experiment. The results showed higher EIF3J-AS1 expression but lower miR-330-5p expression cancer tissues. Furthermore, interfering EIF3J-AS1 increased miR-330-5p and E-cadherin protein expression, leading to a reduction in the proliferation, clone formation, migration, invasion, and N-cadherin protein expression of lung cancer A549 cells. Meanwhile, Transfecting si-EIF3J-AS1 and the miR-330-5p inhibitor could increase the proliferation, clone formation, migration, invasion, and N-cadherin protein expression of lung cancer A549 cells, suggesting the targeted relationship of EIF3J-AS1 to miR-330-5p. In summary, EIF3J-AS1 was highly expressed in lung cancer tissues, and interfering EIF3J-AS1 inhibited the proliferation,migration, and invasion of A549 cells through negative regulation of miR-330-5p.

Background Dual specificity phosphatase 22 (DUSP22), also named as Jun N‐terminal kinase pathway associated phosphatase recently, is reported to be closely engaged in immune and inflammation regulation. This study aimed to investigate the interaction between synovium DUSP22 and serum DUSP22 levels and to explore their correlation with rheumatoid arthritis (RA) risk, inflammation, and disease activity. Methods Synovium and serum samples from 42 RA patients with knee involvement underwent arthroscopy, and 20 knee trauma patients were collected. Besides, serum samples from 40 healthy controls were also obtained. Synovium DUSP22 expression was detected by reverse transcription quantitative polymerase chain reaction, while serum DUSP22 level was detected by enzyme‐linked immunosorbent assay. Results Synovium DUSP22 level was greatly decreased in RA patients compared to trauma controls (p, Synovium and serum samples from 42 RA patients with knee involvement underwent arthroscopy, and 20 knee trauma patients were collected; meanwhile, serum samples from 40 healthy controls were also obtained. Synovium DUSP22 level was greatly decreased in RA patients compared to trauma controls (p

Jiajika in Sichuan, China, is an important mining area for lithium and other Group I and Group II elements. However, the weathered residual overburden makes it difficult to prospect using traditional soil geochemistry. Deep-penetrating geochemical theories provide new ideas and methods that can be used to explore for concealed ore bodies. In this study, topsoil samples were collected from 10 to 25 cm depth above two concealed lithium deposits, Vein 804 (V-804) and Vein X03 (V-X03). Lithium (Li), cesium (Cs), rubidium (Rb), beryllium (Be), and boron (B) were extracted from the soils using pure water and 0.2 mol/L potassium sulfate solutions (K2SO4). Anomalies were observed for water-extractable Li, Cs, and Rb, and K2SO4-extractable Li, Cs, and Be in samples from above both veins. The harmonic mean of the data for each element was used to calculate the response ratio. The highest response ratios are 1.2–2.5 times and 2 to 8 times higher than the response ratios for other samples from V-804 and V-X03, respectively. Linear correlations are observed between the water-extractable and K2SO4-extractable elements, and imply that unbound species of the elements were extracted by K2SO4. The extracted elements display single peak, double peak, and multi-peak anomaly patterns, which indicate that transfer of Li, Cs, Rb, Be, and B through the overburden may be through a combination of diffusion, capillarity, electrochemical forces, and redox gradients.

Imiquimod (Imiq) is a synthetic imizoquinoline compound which can act on Toll-like receptor (TLR)7 and transduce signals involved in cell activation. We investigated the role of Imiq on contact hypersensitivity (CHS) and explored the potential mechanisms of mast cells involved in the process. Topical application of Imiq cream augmented DNFB mediated CHS in C57BL/6 mice. Imiq application induced skin inflammation and increased the number of dendritic cells (DCs) in the draining lymph nodes (DLNs). The splenic cell proliferation to DNBS in DNFB and Imiq treated mice was greater than that in mice of DNFB treatment alone. Peritoneal cell-derived mast cells (PCMCs) expressed TLR7 mRNA. The results from toluidine blue staining for mast cells and histamine detection indicated that Imiq alone did not induce mast cell degranulation while Imiq plus DNFB significantly induced mast cell degranulation. Cromolyn, pyrilamine and cimetidine attenuated CHS reaction induced by Imiq. Our findings suggest that Imiq could augment the intensity of CHS reaction. The mechanisms underlying the effect may relate to histamine release by mast cells and induction of DC homing to DLNs. Blocking histamine action in early time of allergen contact is beneficial to the alleviation of CHS.

BACKGROUND Lung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease. MATERIAL AND METHODS The Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool. RESULTS The GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression - the hub genes - were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1, and ADRB2. In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 were associated with favorable outcomes for LUAD. CONCLUSIONS CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.

Studies on hydrogen leakage have mainly focused on the influences of location and geometrical configuration on the distribution of the hydrogen in various spaces. The present study developed a simplified model for the leakage diffusion of hydrogen in an enclosed cuboid space with two vents, at the top and at the bottom, respectively. The effect of different leakage positions on the diffusion of the hydrogen was analyzed. The results showed that when hydrogen diffused vertically from the bottom to the top of the space, the farther the leakage position was from the vent on the side wall, the more hydrogen accumulated. When the hydrogen leaked in the vertical direction from the floor, the distance between the leakage position and the bottom vent had little effect on the horizontal diffusion speed of the hydrogen at the top of the space. The diffusion speed for the leakage in the horizontal direction was faster than that in the vertical direction. When the hydrogen leaked in the horizontal direction from the side wall, the height of the leakage had little effect on the horizontal diffusion speed of the hydrogen at the top of the space. Stratification occurred for models set up in the present study whenever the envelope of 1% mole fraction, or 4% mole fraction, of hydrogen extended to the whole ceiling.

Hydrogen is one of most attractive clean energy and has been broadly used as fuel for vehicles. However, the accidental leakage of the hydrogen may cause fire and casualties. So, it is extremely important to have a good knowledge of the leaking hydrogen dispersion. This study focuses on the effect of vent amount, location and wind pattern on the distribution of leaked hydrogen using CFD models. The dispersion of high-pressure hydrogen horizontally released from a hydrogen fuel cell transit bus in an enclosure with multiple vents is simulated using CFD models. The results figure out an improvement in ventilation with two vents or forced wind imposed at the vents and the results also illustrate keeping distance between two vents makes the improvement much apparently. The hydrogen mass fraction at monitors closed to the vents that is imposed with the wind keeps low level. As a result, all these kinds of positions are not suggested to be the locations for installing the sensors.

Glycosylphosphatidylinositol-anchored micronemal antigen (GAMA) is an erythrocyte binding protein known to be involved in malarial parasite invasion. Although anti-GAMA antibodies have been shown to block GAMA attachment to the erythrocyte surface and subsequently inhibit parasite invasion, little is known about the molecular mechanisms by which GAMA promotes the invasion process. In this study, LC-MS analysis was performed on the erythrocyte membrane to identify the specific receptor that interacts with GAMA. We found that ankyrin 1 and the band 3 membrane protein showed affinity for GAMA, and characterization of their binding specificity indicated that both Plasmodium falciparum and Plasmodium vivax GAMA bound to the same extracellular loop of band 3 (loop 5). In addition, we show the interaction between GAMA and band 3 was sensitive to chymotrypsin. Furthermore, antibodies against band 3 loop 5 were able to reduce the binding activity of GAMA to erythrocytes and inhibit the invasion of P. falciparum merozoites into human erythrocytes, whereas antibodies against P. falciparum GAMA (PfGAMA)-Tr3 only slightly reduced P. falciparum invasion. The identification and characterization of the erythrocyte GAMA receptor is a novel finding that identifies an essential mechanism of parasite invasion of host erythrocytes.

Remediation of soil contaminated with cadmium (Cd) that can produce rice enriched with selenium (Se) is highly significant for improving the public health in China. A key issue needing resolution in this regard is the simultaneous immobilization of Cd and mobilization of Se. To explore a potential promising method to remediate median-high Se soil that is contaminated by Cd, a potted experiment was conducted, and seven combined amendments (0.03-0.12% lime, 0.03-0.18% bentonite, and 0.3-1.2% biochar of the dry soil weight) were used to immobilize Cd in three paddy soils, in which the concentrations of Cd and Se are 0.46 and 0.45 mg/kg, 1.12 and 0.33 mg/kg, and 2.96 and 0.31 mg/kg, respectively. The soil pH increased by 1.5-2 units after the application of the amendments, and the soil organic carbon (SOC) concentration increased notably with the addition of large quantities of biochar. As the pH and SOC concentration increased, the concentrations of the available Cd in the soil decreased by 35-50%, and the FTIR spectrum showed that O-containing groups and Si-O facilitated the Cd immobilization. The concentration of Cd in brown rice decreased with a decrease in the available Cd. There was no apparent correlation between the Se concentration in the brown rice and the concentration of the available Se in the soil, although the available Se increased by 40-80% after the application of amendments. The accumulation of Se in rice grains was regulated by interactions among the lime, bentonite, biochar, and the soil. An SEM-EDS analysis showed that the biochar particles were covered with bentonite and other soil minerals that could postpone biochar aging and contribute to the longevity of the combined amendments in the soil.

Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.

For decades, cancer metastasis has been a heated topic for its high mortality. Previous research has shown that pre-metastatic niche and metastatic niche are the 2 crucial steps in cancer metastasis, assisting cancerous cells’ infiltration, survival, and colonization at target sites. More recent studies have unraveled details about the specific mechanisms related to the modification of pro-invasion environments. Here, we will review literatures on extracellular matrix (ECM) alterations, general cancer metastasis, organ specificity, pre-metastatic niche, metastatic niche, colony formation and impact on the course of metastasis. Respectively, the metastatic mechanisms like effect of hypoxia or inflammation on pre-metastatic niche construction, as well as the interaction between cancer cells and local milieu will be discussed. Based on the evidences of metastatic niches, we revisit and discussed the “Seed and Soil” hypothesis by Paget. This review will seek to provide insight into the mechanism of metastatic organ specificity which pre-metastatic niche and metastatic niche might suggest from an evolutionary aspect.

Low immunogenicity is one of the major problems limiting the clinical use for DNA vaccines, which makes it impossible to obtain a strong protective immune response after vaccination. In order to explore whether Ag85A DNA vaccine could mount more efficiently protective immune response through new RNA sensor and its signal transduction pathway of antigen presentation we designed and synthesized Ag85A gene fragment containing multiple points mutations and transfected the gene fragment into the dendritic cell line (DC2.4) by CRISPR/Cas9. Subsequently, we focused on the changes of RNA sensors RIG-I, Mda-5, and the downstream adaptors MAVS, IRF3, IRF7 and IFN-β. The results indicated the significant increases in the mRNA and protein expression of RNA sensors RIG-I, Mda-5 and related adaptors MAVS, IRF3, IRF7, and IFN-β in the mutant DC 2.4 cells. The flow cytometry results demonstrated that the expression of MHC II on the surface of DC 2.4 significantly increased when compared with that in control. Therefore, it is suggested that Ag85A mutant DNA could release immunogenic message through RNA sensors and related adaptors via non protein pathway. There is at least one RNA signal transduction pathway of Ag85A DNA in DC2.4 cell. The work provides a new mode of action for nucleic acid vaccine to improve immunogenicity and meaningful data for the better understanding of the mechanisms of DNA vaccine.

Background Obstructive sleep apnea (OSA) increases health risks of cardiovascular disease and stroke. Both genetic factors and environmental exposures contribute to the occurrence of OSA. The purpose of this study was to determine the role of four functional inflammatory single nucleotide polymorphisms (SNPs) (VWF rs1063856, IL‐6 rs1800796, TNF rs1800629, and CRP rs2794521) in the susceptibility and severity of OSA. Methods A case–control study of OSA among Chinese population was conducted. Genotyping was performed using ABI TaqMan SNP genotyping technique. Results We found VWF rs1063856 (OR = 1.50, 95% CIs = 1.10–2.04; p = 0.010), IL‐6 rs1800796 (OR = 1.32, 95% CIs = 1.11–1.56; p = 0.002), TNF rs1800629 (OR = 1.44, 95% CIs = 1.13–1.83; p = 0.003), and CRP rs2794521 (OR = 1.27, 95% CIs = 1.04–1.55; p = 0.021) were all significantly associated with increased susceptibility of OSA, while VWF rs1063856 (OR = 1.75, 95% CIs = 1.18–2.62; p = 0.006), IL‐6 rs1800796 (OR = 1.39, 95% CIs = 1.10–1.76; p = 0.006) were associated with the severity of OSA. Conclusions Our study indicated that functional variants of inflammatory biomarkers could cause the occurrence of OSA and influence the severity of OSA. These findings further support that inflammatory cytokines were closely related to the occurrence and development of OSA.

Background Chronic liver damages from viral infection or alcohol abuse result in liver fibrosis, which is a key pathological event in many types of liver diseases. Discovering new anti-fibrosis agents may provide alternative solutions to manage chronic liver diseases. Methods We first used CCl4 induced liver fibrosis animal model to evaluate the beneficial effects of Cryptotanshinone (CRY). We next explored target miRNAs regulated by CRY in hepatocytes using microarray. The target miRNA candidate was confirmed with realtime-PCR. We also elucidated the downstream target and pathway directly regulated by the miRNA using luciferase assay, western blotting and Epithelial-Mesenchymal Transition (EMT) markers quantification. Lastly, we confirmed CRY induced expression changes of the target genes in vivo. Results CRY oral administration markedly alleviated the liver injury caused by CCl4. miRNAs expression profiling and realtime-PCR validation revealed miR-539-3p was directly induced by CRY around 4 folds. The induction of miR-539-3p suppressed SMO expression and antagonized Hedgehog (Hh) pathway. Independently CRY treatment suppressed SMO and inhibited EMT process in hepatocytes. The CRY induced expression changes of both miR-539-3p (~ 2 folds increase) and SMO (~ 60% decrease) in livers were validated in animal model. Conclusion Our study supported CRY could inhibit liver fibrosis by targeting Hh pathway during EMT. CRY could be used as anti-fibrosis agent candidate for managing chronic liver damages.

Dendritic cell (DC) vaccine is a potent immunotherapeutic approach for cancer treatment, but the clinical efficacy needs to be improved. In this study, we evaluated the combinational effect of Toll-like receptor 7 (TLR7) agonist Imiquimod and BM-DC vaccine against mouse melanoma and explored the potential mechanisms. We found that topical application of Imiquimod cream caused skin inflammation and enhanced exogenous BM-DC homing to draining lymph nodes. Imiquimod treatment enhanced DC vaccine efficacy against B16-OVA melanoma. The combinational modality enhanced cytotoxicity of splenic lymphocyte to tumor cells and inhibited CD4+FOXP3+Treg cell production. TLR7 mRNA expression was confirmed in both MC/9 mast cells and DCs. MC/9 cells treated by R837 (soluble form of Imiquimod) enhanced CD80, CD86, MHC-II and CCR7 expression on DCs. R837 inhibited B16-OVA cell growth in vitro. Our findings suggest that Imiquimod can be used as a potent adjuvant in the formulation of a DC-based tumor fighting vaccine. The mechanisms underlying these effects of Imiquimod are related with enhanced DC homing to DLNs, inhibition of Treg's production, direct tumor cell toxicity and synergistic function with mast cell in enhancing DC activation.

To investigate the therapeutic effect of Toll-like receptor 7( TLR7) agonist imiquimod combined with dendritic cell( DC)-based tumor vaccine on melanoma in mice and the potential mechanism.Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57 BL /6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor( rm GM-CSF) and recombinant mouse interleukin-4( rm IL-4). DC vaccine( OVA-DC) was prepared by overnight incubation of DCs added with chicken ovalbumin. C57 BL /6 mice were separated into four groups which were treated with PBS,topical imiquimod application,OVA-DC intradermal injection and imiquimod plus OVA-DC,respectively. The tumor size was calculated by digital vernier caliper. Peripheral blood CD4~+FOXP3~+Tregs of the tumor-bearing mice was detected by flow cytometry. The cytotoxicity of splenic lymphocyte against B16-OVA was assessed in vitro by CCK-8 assay.Compared with the other three groups,B16-OVA-bearing mice treated with imiquimod plus DC vaccine had the smallest tumor volume. The percentage of CD4~+FOXP3~+Tregs decreased significantly in the combined treated mice. The combined treatment enhanced significantly cytotoxicity of splenic lymphocytes against B16-OVA cells.Imiquimod combined with antigen-pulsed-DC vaccine could reduce CD4~+FOXP3~+Treg proportion and promote anti-tumor effect in mice with melanoma

L-arginine (L-Arg), the precursor of nitric oxide (NO), plays multiple, important roles in nutrient metabolism and immune regulation. Hypoargininemia is one of the distinctive features of malaria patients in endemic areas. To understand the immunoregulatory function of L-Arg in malaria, we investigated the effects of L-Arg, pre- or/and post-treatment, on the cellular/humoral immune response during Plasmodium yoelii 17XL (P.y17XL) infection in DBA/2 mice. Populations of splenic CD4+T-bet+IFN-γ+ T cells (Th1), F4/80+ macrophages, CD4+GATA-3+IL-4+ T cells (Th2), B220+CD138+ plasmacytes and antibody-producing cells (IgG+/IgG1+-plasma cells) were assessed by flow cytometry. Pro-inflammatory cytokines and antibodies (IgG and IgG1) were quantified by immunoassays. We found that treatment with L-Arg significantly decreased parasitemia and shortened disease duration. Prophylactic treatment with L-Arg promotes an enhanced Th1 cell response during the early stages of P.y17XL infection, and treatment with L-Arg in the course of infection facilitates the later humoral immune response. Our findings suggest that treatment with L-Arg may decrease parasite burden and control the host's susceptibility to parasite synchronously by regulating host immune responses against P.y17XL, producing better outcomes for malaria infection. This implies that the supplementation of L-Arg may be a promising adjunctive therapy to reduce malaria-associated mortality in endemic areas.

Fluid machines and control elements such as pumps and valves are widely used in marine piping systems. Pumps and valves are the most important hydrodynamic noise sources in piping systems which present low frequencies and broadband characteristics. Mechanical vibration of pumps and valves transmits along the equipment installation bases and pipeline supports, causing hull vibration and thus noise radiation. The hydrodynamic noise of pumps and valves transmits along the pipeline analogically and then radiates to the sea through the open ends. Mechanical vibration and subsequent noise radiation has been effectively controlled to some extent by active and passive isolation methods. Thus, it becomes an urgent task to eliminate noise radiation from the open ends and through the surrounding fluid. The design of a functional fluid pipeline silencer is imperative, and this kind of fluid pipeline silencer should incorporate low frequency and broadband hydrodynamic noise attenuation characteristics. In this paper, some fluid pipeline elastic-shell silencers with different diameters are proposed based on acoustic-elasticity noise reflecting theory. The acoustic characteristics, such as acoustic impedances and transmission losses of the fluid pipeline silencers, including elastic-shell type and traditional perforated expanding cavity type, are both tested based on acoustic impedance testing techniques. Experimental results indicate that transmission loss (TL) of the elastic-shell silencers can reach 10dB at low frequency broadband 20Hz∼1000Hz. The DN100 elastic-shell silencer with a more compact structure delivers better noise elimination performance than a traditional perforated expanding cavity silencer. Furthermore, all the elastic-shell silencers with different pipe diameters show excellent noise elimination performance at low frequency broadband. Therefore, the elastic-shell silencers could effectively control the hydrodynamic noise of pumps and valves in seawater cooling pipeline systems and reduce nozzle noise radiation. Excellent low frequency and broadband noise elimination characteristics of elastic-shell fluid pipeline silencers are experimentally validated subsequently. The experimental research in this paper provides the basis for future marine applications.

CD59 may inhibit the cytolytic activity of complement by binding to C8/C9 and protect host cell membranes against homologous membrane attack complex (MAC). However, CD59 is widely overexpressed on tumor cells, which has been implicated in tumorigenesis. The active site of CD59 relative to MAC is still confused. As reported the MAC binding site is located in the vicinity of a hydrophobic groove on the membrane distal face of the protein centered around residue W40. Here two site-directed mutagenesis were performed by overlapping extension PCR to delete residue W40 site (Mutant 1, M1) or to change C39W40K41 to W39W40W41 (Mutant 2, M2). Then we constructed mutant CD59 eukaryotic expression system and investigated their biological function on CHO cells compared with wild-type CD59. Stable populations of CHO cells expressing recombinant proteins were screened by immunotechnique. After 30 passages culturing, proteins could be tested. Dye release assays suggest that M1CD59 loses the activity against complement, while M2CD59 increases the anti-complement activity slightly. Results indicate that W40 of human CD59 is important to its activity, and prohibition of this site may be a potential way to increase complement activity and to treat tumors.