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Post-myocardial infarction heart failure (HF) is a major public health concern. Previous studies have reported the critical role of immune response in HF pathogenesis. However, limited studies have reported predictive immune-associated biomarkers for HF. So we attempted to identify potential immune-related indicators for HF early diagnosis and therapy guidance. This study identified two potential immune-related hub genes (IRHGs), namely CXCR5 and FOS, using bioinformatic approaches. The expression levels of CXCR5 and FOS and their ability to predict long-term HF were analyzed. Functional enrichment analysis revealed that the hub genes were enriched in immune system processes, including the interleukin-17 and nuclear factor-kappa B signaling pathways, which are involved in the pathogenesis of HF. Quantitative real-time polymerase chain reaction revealed that the Fos mRNA levels, but not the Cxcr5 mRNA levels, were downregulated in the mice of the HF group. This study successfully identified two IRHGs that were significantly and differentially expressed in the HF group and could predict long-term HF, providing novel insights for future studies on HF and developing novel therapeutic targets for HF.

Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused intestinal villus structural and functional decline is regulated by mTORC1, a sensor of nutrients and growth factors, which is highly activated in intestinal stem and progenitor cells in geriatric mice. These aging phenotypes are recapitulated in intestinal stem cell-specific Tsc1 knockout mice. Mechanistically, mTORC1 activation increases protein synthesis of MKK6 and augments activation of the p38 MAPK-p53 pathway, leading to decreases in the number and activity of intestinal stem cells as well as villus size and density. Targeting p38 MAPK or p53 prevents or rescues ISC and villus aging and nutrient absorption defects. These findings reveal that mTORC1 drives aging by augmenting a prominent stress response pathway in gut stem cells and identify p38 MAPK as an anti-aging target downstream of mTORC1.

In this paper, we propose a vehicle routing problem with time windows (TWVRP). In this problem, we consider a hard time constraint that the fleet can only serve customers within a specific time window. To solve this problem, a hybrid ant colony (HACO) algorithm is proposed based on ant colony algorithm and mutation operation. The HACO algorithm proposed has three innovations: the first is to update pheromones with a new method; the second is the introduction of adaptive parameters; and the third is to add the mutation operation. A famous Solomon instance is used to evaluate the performance of the proposed algorithm. Experimental results show that HACO algorithm is effective against solving the problem of vehicle routing with time windows. Besides, the proposed algorithm also has practical implications for vehicle routing problem and the results show that it is applicable and effective in practical problems. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K2 administration was also reported to be associated with decreased disease activity in RA. Objectives: Immunosuppressive pharmacodynamics of vitamin K2 combined with MTX was investigated. Methods: Mitogen‐activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro. Results: Vitamin K2 alone dose‐dependently suppressed T cell mitogen‐activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5 ng/mL vitamin K2 significantly decreased the IC50 values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465 ng/mL vitamin K2 potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K2 to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4+CD25+ T cells or CD4+CD25+Foxp3+ Treg cells. MTX alone at 100 ng/mL significantly decreased the percentage of CD4+ T cells in PBMCs of healthy subjects (p < 0.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K2 alone tended to suppress the secretion of IL‐17, IFN‐γ, and TNF‐α from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K2 were also observed in combination with MTX. Conclusion: The above information may partially elucidate the potentiation effects of vitamin K2 on the immunosuppressive efficacy of MTX. [ABSTRACT FROM AUTHOR]

Sinomenine (SN) is a plant‐derived alkaloid isolated from Caulis Sinomenii. It has been approved by the State Food and Drug Administration of China for treating rheumatoid arthritis (RA) nearly 20 years ago. To investigate the anti‐RA mechanism of SN, a lot of scholars reported the immunosuppressive effect of SN on T lymphocytes. We continued to evaluate the suppressive function of SN by using human peripheral blood mononuclear cells (PBMCs) isolated from RA patients. As the positive control, 10 ng/ml of methylprednisolone (MP) showed the antiproliferation effect on mitogen‐activated PBMCs of RA patients significantly (*p <.05). Meanwhile, MP decreased the frequency of CD4+ CD25+ T cells and suppressed the secretion of inflammatory Th1/Th2/Th17 cytokines such as IL‐4, IL‐6, IL‐10, IL‐17, IFN‐γ, and TNF‐α. However, SN at concentrations of 0.3–30 μM, showed little suppressive effects on the proliferation of PBMCs of RA patients. We did not observe any suppressive effects of SN on percentages of CD4+ T cells and CD4+ CD25+ T cells in the mitogen‐activated PBMCs of RA patients. The influence of SN on the percentage of CD4+ CD25+ Foxp3+ T cells was also limited. Finally, even 30 μM of SN did not influence the secretion of Th1/Th2/Th17 cytokine significantly. The present study provided evidence that anti‐RA mechanism of SN seems not to be related with the suppressive effects on peripheral T cells. [ABSTRACT FROM AUTHOR]

Background: Over 20 kinds of steroids, tacrolimus ointments, and cyclosporine capsules are usually recommended for the treatment of atopic dermatitis (AD), depending on the symptoms of patients. However, several side effects sometimes occur with the extensive use of these agents for the treatment of pediatric AD patients. The purpose of this study was to explore whether vitamin K2 could be a new immunosuppressive candidate for pediatric patients with AD. Methods: The immunosuppressive efficacy of vitamin K2 was evaluated through a cell‐culture procedure using mitogen‐activated peripheral blood mononuclear cells (PBMCs) obtained from pediatric AD patients. Results: The mean (SD) IC50 value of vitamin K2 for the proliferation of concanavalin A‐activated PBMCs was 15.37 (30.05) μmol/L, while the value for tacrolimus was 0.10 (0.28) ng/mL (0.12 (0.35) nmol/L). There was a significant correlation between the IC50 values for vitamin K2 and those for tacrolimus (P = 0.0001, r = 0.8871). However, there was no significant correlation between the IC50 values of vitamin K2 and those of cyclosporine A or methylprednisolone. A significant correlation between the IC50 values of vitamin K2 or tacrolimus and blood eosinophil counts (P = 0.0099, r = 0.7086 and P = 0.0032, r = 0.7722, respectively) was observed. Conclusion: Vitamin K2‐inhibited T‐cell mitogen stimulated proliferation of PBMCs from pediatric AD patients in a dose‐dependent manner. The PBMCs from pediatric AD patients were more sensitive to the immunosuppressive efficacy of vitamin K2 than the PBMCs from healthy subjects. The individual immunosuppressive pharmacological efficacy of vitamin K2 and of tacrolimus could be inferred from the blood eosinophil count of pediatric AD patients. [ABSTRACT FROM AUTHOR]

This article discusses the factors influencing the yields of molybdenum Kα radiations from a pulsed-power driven needle-and-blade diode for the application of real-time x-ray diffraction of shocked solids. Based on our 300 kV/10 kA pulsed power stand, electrical properties (diode voltage, current and deposited energy) and energy spectrum were evaluated under different diode configurations. It is found that the diode voltage plays an important role in the production of Kα radiation. A large emission angle was beneficial for obtaining higher Kα photon yields and the deposited power on diode could be generally used to predict the Kα radiation. These results are helpful to guide the development of pulsed power diode for dynamic x-ray diffraction applications. [ABSTRACT FROM AUTHOR]