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Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy.

Type I interferons (IFNs) can reprogram the cholesterol biosynthetic pathway to facilitate innate immune responses. In this issue of Immunity, Xiao et al. (2020) reveal that type I IFN signaling and 7-dehydrocholesterol (7-DHC) accumulation form a positive feedback loop to amplify innate immune responses to control viral infections by activating AKT3.

This paper aims to explore the relationship and effect of job-demand-control-support (JDCS) on job burnout, so as to provide evidence for reducing the occurrence of job burnout. It was a cross-sectional descriptive research design adopted, and 290 College English teachers from 10 universities in China were randomly selected to complete a series of questionnaires. The research tools were the Job Content Questionnaire (Chinese Version), Maslach Burnout InventoryEducators Survey (MBI-ES). SPSS 24.0 software was used for statistical analysis by using Pearson correlation analysis and hierarchical regression analysis. The results of this research were as followings: (1) job burnout, job demand, job control of College English teachers were in the upper middle level, social support was below the average; (2) job demand and job burnout were significantly positive correlated with each other (P$\lt \theta.\theta$ 1), job control had significant negatively correlation with job burnout (P$\lt \theta.\theta$1). there was a remarkable negative correlation between job burnout and social support (P$\lt \theta.\theta$1);(3) JDCS model had 82.1% explanatory power on the variance of job burnout. From the research it is shown that the incidence of job burnout of College English teachers is high. The job stress model of JDCS directly affects the job burnout of College English teachers. Certain job control and some support from superiors, colleagues can effectively reduce job burnout of College English teachers.

Recent studies have demonstrated the existence of a discrete pool of cholesterol in the plasma membranes (PM) of mammalian cells-referred to as the accessible cholesterol pool-that can be detected by the binding of modified versions of bacterial cytolysins (e.g., anthrolysin O). When the amount of accessible cholesterol in the PM exceeds a threshold level, the excess cholesterol moves to the endoplasmic reticulum (ER), where it regulates the SREBP2 pathway and undergoes esterification. We reported previously that the Aster/Gramd1 family of sterol transporters mediates nonvesicular movement of cholesterol from the PM to the ER in multiple mammalian cell types. Here, we investigated the PM pool of accessible cholesterol in cholesterol-loaded fibroblasts with a knockdown of Aster-A and in mouse macrophages from Aster-B and Aster-A/B-deficient mice. Nanoscale secondary ion mass spectrometry (NanoSIMS) analyses revealed expansion of the accessible cholesterol pool in cells lacking Aster expression. The increased accessible cholesterol pool in the PM was accompanied by reduced cholesterol movement to the ER, evidenced by increased expression of SREBP2-regulated genes. Cosedimentation experiments with liposomes revealed that the Aster-B GRAM domain binds to membranes in a cholesterol concentration-dependent manner and that the binding is facilitated by the presence of phosphatidylserine. These studies revealed that the Aster-mediated nonvesicular cholesterol transport pathway controls levels of accessible cholesterol in the PM, as well as the activity of the SREBP pathway.

Macrophages reprogram their lipid metabolism in response to activation signals. However, a systems-level understanding of how different pro-inflammatory stimuli reshape the macrophage lipidome is lacking. Here, we use complementary "shotgun" and isotope tracer mass spectrometry approaches to define the changes in lipid biosynthesis, import, and composition of macrophages induced by various Toll-like receptors (TLRs) and inflammatory cytokines. "Shotgun" lipidomics data revealed that different TLRs and cytokines induce macrophages to acquire distinct lipidomes, indicating their specificity in reshaping lipid composition. Mechanistic studies showed that differential reprogramming of lipid composition is mediated by the opposing effects of MyD88- and TRIF-interferon-signaling pathways. Finally, we applied these insights to show that perturbing reprogramming of lipid composition can enhance inflammation and promote host defense to bacterial challenge. These studies provide a framework for understanding how inflammatory stimuli reprogram lipid composition of macrophages while providing a knowledge platform to exploit differential lipidomics to influence immunity.

Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy.

Mice lacking glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) are unable to traffic LPL to the vascular lumen. Thus, triglyceride (TG) clearance is severely blunted, and mice are extremely hypertriglyceridemic. Paradoxically, mice lacking both GPIHBP1 and the LPL regulator, angiopoietin-like 4 (ANGPTL4), are far less hypertriglyceridemic. We sought to determine the mechanism by which Angptl4−/−Gpihbp1−/− double-knockout mice clear plasma TGs. We confirmed that, on a normal chow diet, plasma TG levels were lower in Angptl4−/−Gpihbp1−/− mice than in Gpihbp1−/− mice; however, the difference disappeared with administration of a high-fat diet. Although LPL remained mislocalized in double-knockout mice, plasma TG clearance in brown adipose tissue (BAT) increased compared with Gpihbp1−/− mice. Whole lipoprotein uptake was observed in the BAT of both Gpihbp1−/− and Angptl4−/−Gpihbp1−/− mice, but BAT lipase activity was significantly higher in the double-knockout mice. We conclude that Angptl4−/−Gpihbp1−/− mice clear plasma TGs primarily through a slow and noncanonical pathway that includes the uptake of whole lipoprotein particles.

Objective Angiopoietin-like 4 (ANGPTL4) is a fasting-induced inhibitor of lipoprotein lipase (LPL) and a regulator of plasma triglyceride metabolism. Here, we examined the kinetics of Angptl4 induction and tested the hypothesis that ANGPTL4 functions physiologically to reduce triglyceride delivery to adipose tissue during nutrient deprivation. Methods Gene expression, LPL activity, and triglyceride uptake were examined in fasted and fed wild-type and Angptl4−/− mice. Results Angptl4 was strongly induced early in fasting, and this induction was suppressed in mice with access to food during the light cycle. Fasted Angptl4−/− mice manifested increased LPL activity and triglyceride uptake in adipose tissue compared to wild-type mice. Conclusions Angptl4 is induced early in fasting to divert uptake of fatty acids and triglycerides away from adipose tissues., Highlights •Angptl4 is induced within the first few hours of fasting. •Angptl4 expression is driven by fasting rather than circadian rhythms. •Fasted Angptl4−/− mice have increased triglyceride uptake in adipose tissue. •Angptl4−/− mice also have increased LPL activity specifically in adipose tissue. •Data support a model where ANGPTL4 acts locally in adipose during fasting.

Objective Several members of the angiopoietin-like (ANGPTL) family of proteins, including ANGPTL3 and ANGPTL8, regulate lipoprotein lipase (LPL) activity. Deficiency in either ANGPTL3 or ANGPTL8 reduces plasma triglyceride levels and increases LPL activity, whereas overexpression of either protein does the opposite. Recent studies suggest that ANGPTL8 may functionally interact with ANGPTL3 to alter clearance of plasma triglycerides; however, the nature of this interaction has remained elusive. We tested the hypothesis that ANGPTL8 forms a complex with ANGPTL3 and that this complex is necessary for the inhibition of vascular LPL by ANGPTL3. Methods We analyzed the interactions of ANGPTL3 and ANGPTL8 with each other and with LPL using co-immunoprecipitation, western blotting, lipase activity assays, and the NanoBiT split-luciferase system. We also used adenovirus injection to overexpress ANGPTL3 in mice that lacked ANGPTL8. Results We found that ANGPTL3 or ANGPTL8 alone could only inhibit LPL at concentrations that far exceeded physiological levels, especially when LPL was bound to its endothelial cell receptor/transporter GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1). Physical interaction was observed between ANGPTL3 and ANGPTL8 when the proteins were co-expressed, and co-expression with ANGPTL3 greatly enhanced the secretion of ANGPTL8. Importantly, ANGPTL3–ANGPTL8 complexes had a dramatically increased ability to inhibit LPL compared to either protein alone. Adenovirus experiments showed that 2-fold overexpression of ANGPTL3 significantly increased plasma triglycerides only in the presence of ANGPTL8. Protein interaction assays showed that ANGPTL8 greatly increased the ability of ANGPTL3 to bind LPL. Conclusions Together, these data indicate that ANGPTL8 binds to ANGPTL3 and that this complex is necessary for ANGPTL3 to efficiently bind and inhibit LPL., Highlights • ANGPTL3 by itself is not a potent inhibitor of LPL. • When co-expressed, ANGPTL3 and ANGPTL8 form a complex. • ANGPTL3 facilitates the secretion of ANGPTL8. • ANGPTL3–ANGPTL8 complexes bind to LPL much better than either protein alone. • ANGPTL3 requires ANGPTL8 to efficiently inhibit LPL both in vitro and in vivo.

Macrophages undergo profound metabolic reprogramming in response to activation signals. However, the purpose and the mechanism of this reprogramming remains poorly understood. Cholesterol is an essential lipid molecule that modulates biochemical and biophysical properties of cellular membranes. Microbes have evolved strategies which specifically exploit the presence of membrane cholesterol to facilitate pathogenesis. Cholesterol-dependent cytolysin (CDC) are pore-forming toxins produced by gram-positive microorganisms that results in loss of membrane integrity, cellular dysfunction, and cell death. Herein, we delineate a unappreciated immune cell strategy that relies on rapid reprogramming of cholesterol homeostasis to avoid the deleterious effects CDCs. We show that interferon signals convey resistance to CDCs in myeloid cells by altering the availability of cholesterol in the plasma membrane (PM). Mechanistic studies reveal that resistance to CDCs occurs as a result of the movement of cholesterol from the PM to the endoplasmic reticulum (ER), and ultimately into an intracellular esterified pool. We also find that IFN-mediated inhibition of cholesterol synthesis is required to ensure maximal resistance to CDC challenge. Finally, we demonstrate that the IFN-mediated inhibition of cholesterol synthesis is dependent on production of the oxysterol, 25-hydroxycholesterol, and that the loss of CH25H renders mice more susceptible to CDC-mediated tissue damage. Together, these data provide evidence for remodeling of membrane lipid composition as a host defense strategy to bacterial toxins, and suggests that metabolic reprogramming of lipid architecture has significance beyond that of supporting immune function.

In order to explore the spatial and temporal variations of algal functional groups in the Zipingpu reservoir, a typical channel-type reservoir in the southwest mountainous area of China, water samples were collected from eight sections of the Zipingpu reservoir from April 2016 to March 2017.A total of 21 algal functional groups were identified as B, C, D, F, G, H

From April to July 2012, four species of univalves were selected and 60 samples were chosen from each species of univalves by random sampling in Dandong market. The heavy metal contents of Pb, Cd, Cr, Cu, Zn, total As and total Hg in the edible parts of the univalves were determined by using incomplete digestion - AAS method, and the assessment on the pollution situation of the four species of univalves was made by using the single factor index method. The results showed that bullacta exarata was slightly polluted by Zn, the pollution index was 0.65, and the edible value was threatened, which should be paid attention to. The heavy metal contents in the edible parts of the other univalves were far lower than the pollution limit of the national standard of food safety and the edible value was safe. The heavy metal accumulation ability in bullacta exarata is higher than in the other three species of univalves. Bullacta excta should be the biological indicator for the monitoring of heavy metal pollution.

From April to July 2012, four species of univalves were selected and 60 samples were chosen from each species of univalves by random sampling in Dandong market. The heavy metal contents of Pb, Cd, Cr, Cu, Zn, total As and total Hg in the edible parts of the univalves were determined by using incomplete digestion - AAS method, and the assessment on the pollution situation of the four species of univalves was made by using the single factor index method. The results showed that bullacta exarata was slightly polluted by Zn, the pollution index was 0.65, and the edible value was threatened, which should be paid attention to. The heavy metal contents in the edible parts of the other univalves were far lower than the pollution limit of the national standard of food safety and the edible value was safe. The heavy metal accumulation ability in bullacta exarata is higher than in the other three species of univalves. Bullacta excta should be the biological indicator for the monitoring of heavy metal pollution.

The application of Carboxylmethyl Cellulose Sulfate (CMC-S) in cement paste was studied. The effect of CMC-S on the setting time of cement paste was investigated. Hydration heat of specimens with different cured age was measured via the Hydration Heat Tester (HHT), and hydration process was recorded via Differential Scanning Calorimeter (DSC). The results indicated that CMC-S was a kind of set-retarding and water-reducing agent; its retarding properties appeared at early age, but after three days, the hydration process of cement paste was even improved.

A new type of photovoltaic system with higher generation power density has been studied in detail. The feature of the system is a V-shaped module (VSM) with two tilted monocrystalline solar cells. Compared to solar cells in a flat orientation, the VSM enhances external quantum efficiency and leads to an increase of 31% in power conversion efficiency. Due to the VSM technique, short-circuit current density was raised from 24.94 to 33.7mA/cm(2), but both fill factor and open-circuit voltage were approximately unchanged. For the VSM similar results (about 30% increase) were obtained for solar cells fabricated by using mono-crystal line silicon wafers with only conventional background impurities. (c) 2004 Elsevier B.V. All rights reserved.

The release of fatty acids from plasma triglycerides for tissue uptake is critically dependent on the enzyme lipoprotein lipase (LPL). Hydrolysis of plasma triglycerides by LPL can be disrupted by the protein angiopoietin-like 4 (ANGPTL4), and ANGPTL4 has been shown to inactivate LPL in vitro. However, in vivo LPL is often complexed to glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) on the surface of capillary endothelial cells. GPIHBP1 is responsible for trafficking LPL across capillary endothelial cells and anchors LPL to the capillary wall during lipolysis. How ANGPTL4 interacts with LPL in this context is not known. In this study, we investigated the interactions of ANGPTL4 with LPL-GPIHBP1 complexes on the surface of endothelial cells. We show that ANGPTL4 was capable of binding and inactivating LPL complexed to GPIHBP1 on the surface of endothelial cells. Once inactivated, LPL dissociated from GPIHBP1. We also show that ANGPTL4-inactivated LPL was incapable of binding GPIHBP1. ANGPTL4 was capable of binding, but not inactivating, LPL at 4 °C, suggesting that binding alone was not sufficient for ANGPTL4's inhibitory activity. We observed that although the N-terminal coiled-coil domain of ANGPTL4 by itself and full-length ANGPTL4 both bound with similar affinities to LPL, the N-terminal fragment was more potent in inactivating both free and GPIHBP1-bound LPL. These results led us to conclude that ANGPTL4 can both bind and inactivate LPL complexed to GPIHBP1 and that inactivation of LPL by ANGPTL4 greatly reduces the affinity of LPL for GPIHBP1. Background: Lipoprotein lipase (LPL) function is modified by interactions with its transporter GPIHBP1 and the inhibitor angiopoietin-like 4 (ANGPTL4). Results: ANGPTL4 inactivated GPIHBP1-bound LPL. Inactivated LPL could not bind GPIHBP1. Conclusion: ANGPTL4 inactivation of LPL reduces the affinity of LPL for GPIHBP1 causing dissociation. Significance: Understanding ANGPTL4's interactions with LPL in a physiological context is vital to clarifying ANGPTL4's role in triglyceride metabolism.

Aiming to characteristics of transmission path loss in mobile channel which is caused by complex electromagnetic environment on an open sea area, an improved Irregular Terrain Methodology (ITM)model is proposed in this paper. The algorithm first uses a Two-Path Model to calculate the transmission loss in 1km's distance on maritime; Secondly, the characteristics of radio wave propagation on an open sea was corrected by adding cloud, fog fading and rain loss to the mode; Finally, it compares the results obtained by the standard ITM model and the improved ITM model on Matlab simulation software. The results show that the improved ITM model can better reflect characteristics of pelagic mobile channel and can improve the quality of mobile channel transmission compared with standard ITM model. Keywords-attenuation; path loss simulation;maritime

Shewanella oneidensis is a facultative anaerobic γ-proteobacterium possessing remarkably diverse respiratory capacities for reducing various organic and inorganic substrates. As a veteran research model for investigating redox transformations of environmental contaminants the bacterium is well known to be a naturally ampicillin-resistant microorganism. However, in this study we discovered that ampicillin has a significant impact on growth of S. oneidensis. Particularly, cell lysis occurred only with ampicillin at levels ranging from 0.49 to 6.25 µg/ml but not at 50 µg/ml. This phenotype is attributable to insufficient expression of the β-lactamase BlaA. The subsequent analysis revealed that the blaA gene is strongly induced by ampicillin at high (50 µg/ml), but not at low levels (2.5 µg/ml). In addition, we demonstrated that penicillin binding protein 5 (PBP5), the most abundant low molecular weight PBP (LMW PBP), is the only one relevant to β-lactam resistance under the tested conditions. This nonessential PBP, largely resembling its Escherichia coli counterpart in functionality, mediates expression of the blaA gene.

A new type of photovoltaic system with higher generation power density has been studied in detail. The feature of the proposed system is a V-shaped structure with two polycrystalline solar cells. Compared to solar cells in a conventional approach, the V-shaped structure enhances external quantum efficiency and leads to an increase of 24% in power conversion efficiency.