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Diffuse large B cell lymphoma (DLBCL) is the most common hematological malignancy in adults. Ferroptosis is an iron-dependent programmed cell death caused by lipid peroxidation. However, the potential functions of ferroptosis in the DLBCL prognosis, immune infiltration, and drug resistance remain unknown. Data of DLBCL patients were downloaded from public GEO databases and TCGA cohort. R software was used for analysis. Ferroptosis-related risk score model was constructed using LASSO Cox regression analysis. The prognosis of the model and its association with immune cells infiltration and ibrutinib-resistance were studied by single-sample gene set enrichment analysis (ssGSEA) and correlation analysis. Ferroptosis-related risk score model was constructed with 11 ferroptosis-related genes. DLBCL patients can be divided into high- or low-risk groups with this model. High-risk patients had significant shorter survival (p 0.001). The area under curve at 3-year was 0.779. Functional enrichment analysis was mainly associated with the immune response. High score patients were positively correlated with immunosuppressive cell infiltration, including macrophages and regulatory T cells, and immunoevasion checkpoints, such as CTLA4, PD-L1, LAG-3, and TIM-3. We also found that tumors with high risk would resist to ibrutinib treatment and uncovered that acetaminophen, as a ferroptosis inducer, inhibited the defined high-risk gene expression in the ibrutinib-resistant DLBCL cell lines. Ferroptosis-related risk score model can predict the overall survival (OS) of DLBCL patients and ibrutinib resistance of ABC-DLBCL cells, which was associated with immunosuppression status within the tumor microenvironment.

Appropriate migration of cytotoxic T effector cells into the tumors is crucial for their antitumor function. Despite the controversial role of PI3K-Akt in CD8+ T cell mTORC1 activation, a link between Akt-mTORC1 signaling and CD8+ trafficking has been demonstrated. We have recently discovered that TCR-induced calcineurin activates DAPK1, which interacts with TSC2 via its death domain and phosphorylates TSC2 via its kinase domain to mediate mTORC1 activation in CD8+ T cells. However, whether DAPK1 regulates CD8+ trafficking into tumors remains unclear. Here, using pharmacological inhibitor and genetic approaches, we found that like rapamycin, inhibition of DAPK1 activity led to enhanced expression of the homing receptors CD62L and CCR7. Deletion of either kinase domain or death domain in the T cell compartment reduced the T cell activation and maintained the expression of CD62L and CCR7. DAPK1-DD-deficient mice were more susceptible to tumor growth and deficiency of DAPK1 activity significantly reduced the migratory ability of CD8+ into the tumors. These data revealed a crucial role of DAPK1-mTORC1 in mediating CD8+ trafficking and antitumor function.

Purpose Macrophages are important regulators of environmental allergen-induced airway inflammation and asthma. ATP6V0d2 is a subunit of vacuolar ATPase highly expressed in macrophages. However, the functions of ATP6V0d2 in the regulation of pathogenesis of allergic asthma remain unclear. The aim of this study is to determine the function and related molecular mechanisms of macrophage protein ATP6V0d2 in allergic asthma. Methods We compared the disease severity between female C57BL/6 wild-type and ATP6V0d2-/- mice in an ovalbumin (OVA)-induced asthma model. We also investigated the association of expression of ATP6V0d2, PU.1 and CCL17 with disease severity among asthmatic patients. Results The expression of ATP6V0d2 in sputum cells of asthmatic patients and in the lungs of OVA-challenged mice was enhanced compared to healthy subjects and their counterparts, respectively. However, ATP6V0d2-deficient mice exaggerated inflammatory cell infiltration as well as enhanced alternative activated macrophage (AAM) polarization and mucus production in an OVA-induced asthma model. Furthermore, we found that Atp6v0d2 promoted lysosomal degradation of Pu.1, which induced AAM polarization and Ccl17 production. Among asthma patients, ATP6V0d2 expression was inversely associated with disease severity, whereas PU.1 and CCL17 expression was positively associated with disease severity. Conclusions Our results identify macrophage Atp6v0d2, as an induced feedback inhibitor of asthma disease severity by promoting Pu.1 lysosomal degradation, which may in turn leads to reduced AAM polarization and Ccl17 production.

Stem bending during vase time is a major problem in many cultivars of cut gerbera flowers. In this study, we focused on the involvement of postharvest bacteria and evaluated the efficacy of nano-silver (NS) in reducing bacterial proliferation and stem bending in cut gerbera ‘Real’ flowers in vitro and in vivo. Four species of dominant bacteria, Pseudomonas sp., Acinetobacter junii, Bacillus stearothermophilus, and Myroides sp., were isolated from the stem ends of cut gerberas. Exogenous addition of 3–5 log10 colony forming units (CFU) mL−1 of each bacterial species resulted in a sharp reduction in vase life, relative fresh weight, and water uptake of cut gerbera flowers. However, Pseudomonas sp. had little impact on their vase life and ornamental quality at concentrations of 3–4 log10 CFU mL−1. In vitro assessments showed that the minimum inhibitory concentrations (MICs) of NS for both A. junii and Myroides sp. were 2.5 mg L−1, and NS MICs for B. stearothermophilus and Pseudomonas sp. were 5 and 7.5 mg L−1, respectively. Additionally, compared with the control, pretreatment with 5 and 10 mg L−1 NS for 24 h nearly doubled the vase life of cut gerberas, maintained their relative fresh weight, and improved water uptake. Furthermore, scanning electron microscopy revealed that the NS pretreatment reduced bacterial colonization on the stem ends. Overall, our findings indicate that all four genera of dominant bacterial species isolated from the stem ends of cut gerberas are involved in stem bending, and NS pretreatment effectively alleviated bacteria-induced xylem blockage and improved water uptake, thereby reducing the incidence of stem bending and extending the vase life of cut gerberas.

Appropriate migration of cytotoxic T effector cells into the tumors is crucial for their antitumor function. Despite the controversial role of PI3K-Akt in CD8

Mechanistic target of rapamycin complex 1 (mTORC1) regulates CD8(+) T-cell differentiation and function. Despite the links between PI3K-AKT and mTORC1 activation in CD8(+) T cells, the molecular mechanism underlying mTORC1 activation remains unclear. Here, we show that both the kinase activity and the death domain of DAPK1 are required for maximal mTOR activation and CD8(+) T-cell function. We found that TCR-induced activation of calcineurin activates DAPK1, which subsequently interacts with TSC2 via its death domain and phosphorylates TSC2 to mediate mTORC1 activation. Furthermore, both the kinase domain and death domain of DAPK1 are required for CD8(+) T-cell antiviral responses in an LCMV infection model. Together, our data reveal a novel mechanism of mTORC1 activation that mediates optimal CD8(+) T-cell function and antiviral activity.

Peripheral naive CD4+ and CD8+ cells are developed in the thymus and proliferate and differentiate into various specialized T cell subsets upon activation by peptide-major histocompatibility complexes in periphery to execute different functions during immune responses. Cytokines, transcription factors, and a large number of intracellular molecules have been shown to affect T cell development, activation, and function. In addition, epigenetic modifications, such as histone modification and DNA methylation, regulate T cell biology. The epigenetic modifications are regulated by a range of DNA methyltransferases, DNA demethylation enzymes, and histone modification enzymes. Dysregulations of epigenetic modifications are closely associated with autoimmune diseases and tumorigenesis. Here, we review the current literature about the functions of DNA and histone modification enzymes in T cell development, activation, differentiation, and function.

Macrophages perform key functions in tissue homeostasis that are influenced by the local tissue environment. Within the tumor microenvironment, tumor-associated macrophages can be altered to acquire properties that enhance tumor growth. Here, we found that lactate, a metabolite found in high concentration within the anaerobic tumor environment, activated mTORC1 that subsequently suppressed TFEB-mediated expression of the macrophage-specific vacuolar ATPase subunit ATP6V0d2. Atp6v0d2(–/–) mice were more susceptible to tumor growth, with enhanced HIF-2α–mediated VEGF production in macrophages that display a more protumoral phenotype. We found that ATP6V0d2 targeted HIF-2α but not HIF-1α for lysosome-mediated degradation. Blockade of HIF-2α transcriptional activity reversed the susceptibility of Atp6v0d2(–/–) mice to tumor development. Furthermore, in a cohort of patients with lung adenocarcinoma, expression of ATP6V0d2 and HIF-2α was positively and negatively correlated with survival, respectively, suggesting a critical role of the macrophage lactate/ATP6V0d2/HIF-2α axis in maintaining tumor growth in human patients. Together, our results highlight the ability of tumor cells to modify the function of tumor-infiltrating macrophages to optimize the microenvironment for tumor growth.

The performance of bubble column humidifier and dehumidifier is investigated experimentally under sub-atmospheric pressures for the humidifier and elevated pressures for the dehumidifier. The bubble columns examined are of 10 cm diameter and 25 cm height. They are equipped with internal cooling and heating coils and the air is sparged through perforated plates at its bottom. The pressure tested in the humidifier ranges from 7 psia (0.48 bar) to 15 psia (1.03 bar), while the pressure tested in the dehumidifier ranges from 15 psia (1.03 bar) to 30 psia (2.07 bar). In addition, the water level in the bubble columns and the superficial velocity were varied in the range of 5–7 cm and 2–20 cm/s respectively. The performance was evaluated by measuring the total heat transfer rate and the effectiveness. Moreover, the experimental values of the mass transfer coefficient are presented as a function of the superficial velocity and pressure. The results show that operating the bubble column humidifier at sub-atmospheric pressure enhances the total heat transfer by about 35% and the effectiveness by about 7.1%. However, operating the dehumidifier at elevated pressures, results in higher heat transfer rate by about 27% but lower effectiveness by about 3.2%. It was demonstrated that the liquid height in the column has no significant effect on the performance however; the superficial velocity increases both the heat transfer and effectiveness for the humidifier and dehumidifier. Moreover, a modified effectiveness-number of transfer units (e-NTU) model for counter flow cooling tower was found to agree well with the experimental results of the effectiveness and NTU. The e-NTU model is an effective approach to analyze the performance of bubble column humidifier and dehumidifier.

Many experimental and theoretical studies have been conducted on bubble columns to improve its performance. Most of these studies assumed operating under atmospheric pressure condition and neglected the gas-side resistance. In this work, the effect of the pressure on the dehumidification process in bubble column dehumidifier is investigated experimentally under varying operating conditions. The measurements were conducted at absolute pressures in the range of 1–2 bars, superficial velocity range of 2–18 cm/s, and column height range of 3–7 cm. A model is developed for the relationship between the bubble column effectiveness and the number of transfer units which combines the influence of the heat and mass transfer processes. In addition, a semi-empirical model is adopted and modified for the gas-side mass transfer coefficient to capture the effect of the pressure. The model correlates Sherwood number with Reynolds number, Schmidt number, and the density ratio of air and water vapor. It is found that the total heat transfer rate and the effectiveness of the bubble column dehumidifier both increase with the superficial velocity. However, the heat transfer rises and the effectiveness decreases with the pressure. The column height is found to insignificantly affect the heat transfer and the effectiveness. The developed models predict the total heat transfer rate and the bubble column effectiveness with a maximum deviation of 2% from the experimental measurements. The results suggest that operating a bubble column dehumidifier under higher pressure will result in a larger size to compensate for the decrease occurs in the effectiveness.

This paper presents an application of the canonical duality theory for box constrained nonconvex and nonsmooth optimization problems. By use of the canonical dual transformation method, which is developed recently, these very difficult constrained optimization problems inRncan be converted into the canonical dual problems, which can be solved by deterministic methods. The global and local extrema can be identified by the triality theory. Some examples are listed to illustrate the applications of the theory presented in the paper.

Skin lesion is the second common clinical manifestations of systemic lupus erythematosus (SLE), but its pathogenesis is not clear. IL-1 is a proinflammatory cytokine, and its role in SLE skin lesion is still unclear. We used IL-1R deficient mice and other gene deficient mice to study the role of IL-1 in the lupus serum -induced skin inflammation. We found that the severity of skin inflammation induced by lupus serum was significantly reduced in IL-1R deficient mice and caspase-1 deficient mice. IL-1R deficiency did not affect the expression of FcγRI (CD64), FcγRII (CD32) and MHC class II (CD74) induced by lupus serum. IL-1R deficiency also reduced the lipid raft clustering, and decreased expression of MCP-1 and TNFa in monocytes. Skin inflammation and keratinocyte proliferation were significantly decreased in TNFa deficient mice. Our findings indicate that IL-1 plays an important role in skin lesions of SLE. This study suggests that IL-1 is a therapeutic target in skin lesions of SLE.

Skin injury is the second most common clinical manifestation in patients with systemic lupus erythematosus (SLE). Estrogen may affect the onset and development of SLE. In this study, we investigated the role of estrogen and its membrane receptor GPER1 in SLE-related skin injury in mice treated with SLE serum in vivo, and monocytes from mouse spleen in vitro. We found that skin injury induced by SLE serum was more severe in female mice and required monocytes. Estrogen promoted these effects through the membrane receptor GPER1 located in lipid rafts and that inhibition of lipid rafts and GPER1 suppressed SLE serum-induced skin inflammation and expression of inflammatory molecules. From these studies, we conclude that estrogen promotes the development of skin injury induced by SLE serum through the membrane receptor GPER1 and that lipid rafts play an important role in the regulatory effect of GPER1 in SLE skin inflammation.

The antibacterial and antifungal properties of the ethanol extract of Erigeron breviscapus whole plant was evaluated. The extract showed a moderate antibacterial activity and a high antifungal activity.