Apolipoprotein E deficiency potentiates macrophage against Staphylococcus aureus in mice with osteomyelitis via regulating cholesterol metabolism

IntroductionStaphylococcus aureus (S. aureus) osteomyelitis causes a variety of metabolism disorders in microenvironment and cells. Defining the changes in cholesterol metabolism and identifying key factors involved in cholesterol metabolism disorders during S. aureus osteomyelitis is crucial to understanding the mechanisms of S. aureus osteomyelitis and is important in designing host-directed therapeutic strategies.MethodsIn this study, we conducted in vitro and in vivo experiments to define the effects of S. aureus osteomyelitis on cholesterol metabolism, as well as the role of Apolipoprotein E (ApoE) in regulating cholesterol metabolism by macrophages during S. aureus osteomyelitis.ResultsThe data from GSE166522 showed that cholesterol metabolism disorder was induced by S. aureus osteomyelitis. Loss of cholesterol from macrophage obtained from mice with S. aureus osteomyelitis was detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS), which is consistent with Filipin III staining results. Changes in intracellular cholesterol content influenced bactericidal capacity of macrophage. Subsequently, it was proven by gene set enrichment analysis and qPCR, that ApoE played a key role in developing cholesterol metabolism disorder in S. aureus osteomyelitis. ApoE deficiency in macrophages resulted in increased resistance to S. aureus. ApoE-deficient mice manifested abated bone destruction and decreased bacteria load. Moreover, the combination of transcriptional analysis, qPCR, and killing assay showed that ApoE deficiency led to enhanced cholesterol biosynthesis in macrophage, ameliorating anti-infection ability.ConclusionWe identified a previously unrecognized role of ApoE in S. aureus osteomyelitis from the perspective of metabolic reprogramming. Hence, during treating S. aureus osteomyelitis, considering cholesterol metabolism as a potential therapeutic target presents a new research direction

Study on the effect of multi-source solid waste on the performance of its backfill slurry

The preparation of slurry from multi-source solid waste for underground backfill adds a way out for solid waste disposal, which is beneficial to reduce environmental impact. In this paper, the effects of gangue, fly ash, gasification coarse slag and desulfurization gypsum on the fluidity, early strength, thermal stability and other properties of the backfill slurry were studied by fluidity test, strength test, Thermo-Gravimetric Analysis (TGA), Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD). The results show that: (1) When G/SW (mass ratio of gangue to solid waste) < 23%, gangue is beneficial to improve the fluidity and early strength of backfill slurry; with the increase of fly ash content, the fluidity of backfill slurry decreases, but its early strength increases; gasification coarse slag has a negative effect on the fluidity of backfill slurry, but it is beneficial to its early strength when GCS/SW (mass ratio of gasification coarse slag to solid waste) < 33%; desulfurization gypsum can improve the fluidity of the backfill slurry, but it is not conducive to the increase of early strength. (2) The compression failure mode of the backfill is mainly divided into the crack-intensive failure, the single main crack penetration splitting failure, and the double main crack conjugate splitting failure. (3) Endothermic dehydration reactions of adsorbed water and crystallization water generally occur at 55–65 °C and 110–130 °C for backfill with different solid waste contents; As the temperature continues to increase, the backfill material undergoes a slow exothermic decomposition reaction; Increasing the content of gangue, fly ash and gasification coarse slag and reducing the content of desulfurized gypsum can make the backfill less weight loss at high temperature and better thermal stability. (4) The main mineral phases in the backfill material are gypsum and quartz, and there are also a small amount of acicular and hexagonal hydration products thaumasite. After high temperature, the thaumasite is dehydrated and decomposed. The research results are helpful to deeply understand the performance of multi-source solid waste for underground backfilling

Daidzein alleviates osteoporosis by promoting osteogenesis and angiogenesis coupling

Background Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target. Methods Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis. Results Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs. Conclusions This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason

Prediction model and its application of helium extraction OPEX based on response surface methodology

Focusing on the situation of the low helium content in natural gas resource in China and the high cost of helium extraction, the OPEX prediction model of helium extraction that based on the Response Surface Methodology (RSM) is proposed. This method applies ASPEN-HYSYS software to simulate the helium extraction process flow for a given product composition, pressure, and temperature; Applying the Design Expert module for Response Surface Methodology(RSM) parameter design, combined with OPEX of existing projects, determine the key influencing factors and upper and lower limits of OPEX, and obtaining the corresponding OPEX for different parameter values; Applying the Box Behnken Design (BBD) principle to optimize the helium extraction process parameters of RSM, based on fitting results and parameter significance verification of second-order regression function, the OPEX prediction model is built.This method is applied to a domestic helium extraction project, and the unit helium extraction cost is between 100 and 119.52 yuan/m3, IRR is 13.37%. The result shows the project has economic benefit, and the method presents a good perspective application

Effects of Enclosure Succession on the Morphological Characteristics and Nutrient Content of a Bamboo Whip System in a Moso Bamboo (<i>Phyllostachys edulis</i>) Forest on Wuyi Mountain, China

To investigate the morphological characteristics and nutrient content of bamboo whip systems in the Wuyi Mountain Moso bamboo (Phyllostachys edulis) forest in response to enclosure succession. The mixed Moso bamboo forests in the Wuyi Mountain Nature Reserve with 0, 4, 6, 11, 16, and 41 enclosure years were taken as the object of investigation. All the bamboo whips in the 2 m × 2 m sample plots were excavated layer-by-layer according to the soil layers of 0–20 cm, 20–40 cm, and 40–60 cm, and a total of 54 plots were dug. The morphological characteristics and nutrient contents of the Moso bamboo whips in the different soil layers were analyzed and evaluated. Enclosure management measures can not only effectively improve vegetation coverage, biodiversity, and biomass, but also improve soil moisture and nutrient status, indirectly affecting the vegetation, which is of great significance for preventing soil erosion. The results showed that the whip number, whip diameter, flagella number, whip length, and whip weight in the 0–20 cm soil layer were significantly increased by 169.2%, 11.0%, 197.5%, 113.7%, and 109.0% (p p p p p p p p p p < 0.05). In summary, enclosure measures were implemented for Moso bamboo forests in the Wuyi Mountain Nature Reserve, which promote the growth of Moso bamboo whips and optimize the structure of bamboo whips

DataSheet_1_Apolipoprotein E deficiency potentiates macrophage against Staphylococcus aureus in mice with osteomyelitis via regulating cholesterol metabolism.docx

IntroductionStaphylococcus aureus (S. aureus) osteomyelitis causes a variety of metabolism disorders in microenvironment and cells. Defining the changes in cholesterol metabolism and identifying key factors involved in cholesterol metabolism disorders during S. aureus osteomyelitis is crucial to understanding the mechanisms of S. aureus osteomyelitis and is important in designing host-directed therapeutic strategies.MethodsIn this study, we conducted in vitro and in vivo experiments to define the effects of S. aureus osteomyelitis on cholesterol metabolism, as well as the role of Apolipoprotein E (ApoE) in regulating cholesterol metabolism by macrophages during S. aureus osteomyelitis.ResultsThe data from GSE166522 showed that cholesterol metabolism disorder was induced by S. aureus osteomyelitis. Loss of cholesterol from macrophage obtained from mice with S. aureus osteomyelitis was detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS), which is consistent with Filipin III staining results. Changes in intracellular cholesterol content influenced bactericidal capacity of macrophage. Subsequently, it was proven by gene set enrichment analysis and qPCR, that ApoE played a key role in developing cholesterol metabolism disorder in S. aureus osteomyelitis. ApoE deficiency in macrophages resulted in increased resistance to S. aureus. ApoE-deficient mice manifested abated bone destruction and decreased bacteria load. Moreover, the combination of transcriptional analysis, qPCR, and killing assay showed that ApoE deficiency led to enhanced cholesterol biosynthesis in macrophage, ameliorating anti-infection ability.ConclusionWe identified a previously unrecognized role of ApoE in S. aureus osteomyelitis from the perspective of metabolic reprogramming. Hence, during treating S. aureus osteomyelitis, considering cholesterol metabolism as a potential therapeutic target presents a new research direction.</p