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Fungicide-resistant Fusarium has become a threaten to wheat production. Novel fungicide formulations can improve the efficacy of active ingredient and minimize the emergence of resistance. Encapsulation of fungicides in biodegradable carriers, especially, in polysaccharide, is a feasible approach to develop environment-friendly and efficient formulation. This study focused on the synthesis of ethyl cellulose-based phenamacril nano-delivery system by combining emulsion-solvent evaporation and high-pressure homogenization technology to improve the control of fusarium head blight in wheat. Emulsifier 125 and Tersperse 2500 were screened from eleven commonly used surfactants. Emulsifier 125 and Tersperse 2500 in a ratio of 2:1 and phenamacril nanocapsules with the mean particle size of 152.5 ± 1.3 nm were prepared. These showed excellent storage stability and wettability on crop leaves. A bioassay comparing the nanocapsules with a commercial preparation against Fusarium graminearum showed significantly improved biological activity. This formulation could be used to effectively not only to control fusarium head blight but also delay the occurrence of resistance.

Pesticide compounding technology for disease and pest control emerges as an effective way to increase the effectiveness of pesticides while reducing pesticides resistance. Nanomaterials and encapsulation technology have offered a new insight into preparing efficient pesticide formulations, especially constructing a co-delivery nanoparticle for synergistic pesticides. In this study, a dinotefuran/avermectin co-delivery nanoparticles (DACNPs) against pear tree pests with polylactic acid (PLA) as the wall material were constructed by double-emulsion method combined with high-pressure homogenization technique. The drug content of the DACNPs was 39.1% with an average size of 245.7 ± 4.2 nm and the mean polymer dispersity index (PDI) value was 0.123. The DACNPs showed high foliar retention and good spread performance on target leaves due to the nanoscale effect. The obtained DACNPs showed a better control effect on Grapholitha molesta Busck and Psylla chinensis Yang et Li compared with the commercial formulations, which could significantly prolong the effective duration and enhance the bioactivity with lower amounts and application frequency of pesticides. This study may provide new insights into developing novel pesticide formulations to improve the utilization rate of pesticides, reduce environmental pollution and minimize the cost of farming.

Lipopolysaccharide (LPS) poses a considerable threat to food safety and human health. A colorimetric assay for LPS detection based on LPS binding aptamer (LBA) and SYBR Green I (SG) mediated aggregation of gold nanoparticles (AuNPs) was established. In the absence of LPS, the LBA was absorbed onto the AuNPs surface which prevented SG-induced aggregation of AuNPs, and the sensing system exhibited red color. When LPS was added, it interacted with the LBA, forming a complex. At higher LPS concentration, many LBAs were exhausted resulting in SG-induced aggregation of AuNPs, and color change from red to blue. The range of colorimetric detection of LPS was linear in 0-12 EU/mL, with a limit of detection of 0.1698 EU/mL. Spiked LPS in real samples and interfering substances were also identified. This assay ingeniously using the fluorescent dye SG as an effective trigger of AuNPs aggregation, is rapid and facile than most of those earlier reported LBA-based LPS assays, and there is potential to be modified to construct assays for other targets.

The rapid fall in blood pressure following unclipping of the stenotic renal artery in the Goldblatt two-kidney one-clip (2K1C) model of renovascular hypertension is proposed to be due to release of renomedullary vasodepressor lipids, but the mechanism has remained unclear. In this study, we hypothesized that the hypotensive response to unclipping is mediated by exosomes released from the renal medulla. In male C57BL6/J mice made hypertensive by the 2K1C surgery, unclipping of the renal artery after 10 days decreased mean arterial pressure (MAP) by 23 mmHg one hr after unclipping. This effect was accompanied by a 556% increase in the concentration of exosomes in plasma as observed by nanoparticle tracking analysis. Immunohistochemical analysis of exosome markers, CD63 and AnnexinII, showed increased staining in interstitial cells of the inner medulla of stenotic but not contralateral control kidney of clipped 2K1C mice. Treatment with rapamycin, an inducer of exosome release, blunted the hypertensive response to clipping, whereas GW-4869, an exosome biosynthesis inhibitor, prevented both the clipping-induced increase in inner medullary exosome marker staining and the unclipping-induced fall in MAP. Plasma exosomes isolated from unclipped 2K1C mice showed elevated neutral lipid content compared to sham mouse exosomes by flow cytometric analysis after Nile red staining. Exosomes from 2K1C but not sham control mice exerted potent MAP-lowering and diuretic-natriuretic effects in both 2K1C and angiotensin II-infused hypertensive mice. These results are consistent with increased renomedullary synthesis and release of exosomes with elevated antihypertensive neutral lipids in response to increased renal perfusion pressure.

The activation of transient receptor potential canonical 6 (TRPC6) channel participates in the glomerulosclerosis. The TRPC6 also participates in the mechanical or pressure sensation in various cel...

Kidney is the major organ responsible for long term regulation of blood pressure. Impaired renal sodium excretion and perfusion pressure is main driver of hypertension. This perfusion pressure and ...

The disruption in transportation of oxLDL‐derived cholesterol and the subsequent lipid accumulation in macrophages are the hallmark events in atherogenesis. Our recent studies demonstrated that lysosomal Ca2+ messenger of nicotinic acid adenine dinucleotide phosphate (NAADP), an enzymatic product of CD38 ADP‐ribosylcyclase (CD38), promoted lipid endocytic trafficking in human fibroblast cells. The current studies are designed to examine the functional role of CD38/NAADP pathway in the regulation of lysosomal cholesterol efflux in atherosclerosis. Oil red O staining showed that oxLDL concentration‐dependently increased lipid buildup in bone marrow‐derived macrophages from both wild type and CD38−/−, but to a significant higher extent with CD38 gene deletion. Bodipy 493/503 fluorescence staining found that the deposited lipid in macrophages was mainly enclosed in lysosomal organelles and largely enhanced with the blockade of CD38/NAADP pathway. Filipin staining and direct measurement of lysosome fraction further revealed that the free cholesterol constituted a major portion of the total cholesterol segregated in lysosomes. Moreover, in situ assay disclosed that both lysosomal lumen acidity and the acid lipase activity were reduced upon cholesterol buildup in lysosomes. In CD38−/− mice, treatment with Western diet (12 weeks) produced atherosclerotic damage in coronary artery with striking lysosomal cholesterol sequestration in macrophages. These data provide the first experimental evidence that the proper function of CD38/NAADP pathway plays an essential role in promoting free cholesterol efflux from lysosomes and that a defection of this signalling leads to lysosomal cholesterol accumulation in macrophages and results in coronary atherosclerosis in CD38−/− mice.

The present study was designed to test the hypothesis that cyclic-ADP-ribose (cADPR) serves as a novel second messenger to mediate intracellular Ca2+ concentration in As4.1 cells, a prototy

Our recent studies have demonstrated that the buildup of oxLDL-derived free cholesterol (FC) in macrophages profoundly contributes to the foam cell formation and coronary artery atherosclerosis in ...

Cyclic-ADP-ribose (cADPR) has been reported to serve as a second messenger to mobilize intracellular Ca2+ independent of IP3 in a variety of mammalian cells. This cADPR-mediated Ca2+ signaling pathway importantly participates in the regulation of various cell functions. The present study determined the role of endogenous cADPR in mediating ryanodine-sensitive Ca2+-induced Ca2+ release (CICR) in vascular myocytes from small renal arteries and vasomotor response of these arteries. In freshly-isolated renal arterial myocytes, addition of CaCl2 (0.01, 0.1, and 1 mM) into the Ca2+-free bath solution produced a rapid Ca2+ release response from the sarcoplasmic reticulum (SR), with a maximal increase of 237+/-25 nM at 1 mM CaCl2. This CaCl2 response was significantly blocked by a cell-membrane permeant cADPR antagonist, 8-bromo-cADP-ribose (8-br-cADPR) (30 microM) or ryanodine (50 microM). Caffeine, a classical CICR or ryanodine receptor activator was found to stimulate the SR Ca2+ release (Delta[Ca2+]i: 253+/-35 nM), which was also attenuated by 8-br-cADPR or ryanodine. Using isolated and pressurized small renal arteries bathed with Ca2+-free solution, both CaCl2 and caffeine-induced vasoconstrictions were significantly attenuated by either 8-br-cADPR or ryanodine. Biochemical analyses demonstrated that CaCl2 and caffeine did not increase cADPR production in these renal arterial myocytes, but confocal microscopy showed that a dissociation of the accessory protein, FK506 binding protein 12.6 (FKBP12.6) from ryanodine receptors was induced by CaCl2. We conclude that cADPR importantly contributes to CICR and vasomotor responses of small renal arteries through enhanced dissociation of ryanodine receptors from their accessory protein.

We recently reported that NADH oxidase is one of the major enzymes responsible for superoxide (O[Formula: see text]·) production in the rat kidney. However, the functional significance of NADH oxidase-mediated O[Formula: see text]· production and the mechanisms regulating this enzyme activity are poorly understood. Using fluorescence microscopic imaging analysis, the present study demonstrated that thick ascending limbs of Henle's loop (TALHs) exhibited red fluorescence when incubated with dihydroethidium (DHE), suggesting that O[Formula: see text]· is produced in this tubular segment. Compared with other nephron segments, TALHs from both renal cortex and medulla showed the highest fluorescence intensity. By incubating cortical TALHs (cTALHs) with the substrates of NADH oxidase, xanthine oxidase, nitric oxide synthase, arachidonic acid-metabolizing enzymes, and intramitochondrial oxidases, NADH oxidase was found to be one of the most important enzymes for O[Formula: see text]· production in this tubular segment. The NADH oxidase inhibitor diphenyleneiodonium (DPI; 100 μM) completely blocked NADH-induced O[Formula: see text]· production in cTALHs. Exposure of cTALHs to low Po2(5–10 Torr) significantly increased O[Formula: see text]· production regardless of the absence or presence of NADH. Furthermore, angiotensin II (100 nM) increased NADH oxidase activity by 32%, which was completely blocked by DPI. These results suggest that NADH oxidase is a major enzyme responsible for O[Formula: see text]· production in the TALHs and that the production of O[Formula: see text]· via NADH oxidase may be regulated by renal tissue oxygenation and circulating hormones.

Activation of NALP3 inflammasome has been shown to be involved in various renal pathological conditions. It remains unknown whether renal NALP3 inflammasome activation participates in the abnormal renal response to high salt diet in Dahl salt sensitive rats. In addition, whether inhibition of NALP3 inflammasome activation contributes to the renal protective actions of stem cells is not clear. The present study detected the response of NALP3 inflammasome to high salt intake and determined the effect of mesenchymal stem cell (MSC) transplantation on inflammasome activation. Immunostaining showed that 3 essential components of the NALP3 inflammasome, NALP3, ASC and caspase-1, were all mainly present in distal tubules and collecting ducts. Interestingly, the renal medullary mRNA and protein levels of these inflammasome components were remarkably increased by 2-4 fold in response to high salt intake in Dahl S rats, while remained no change in normal rats. High salt-induced increases of renal medullar inflammas...

It is well accepted that statins, hypercholesterol-lowing agents, have direct therapeutic effects on the atherosclerotic lesions. However, the underlying mechanism remains unknown. Given the pivota...

Niacin (Nicotinic acid), a hyperlipidemia-lowering agent, acts as a substrate in the enzymatic synthesis of lysosomal Ca2+ messenger, NAADP by CD38. Our recent studies have demonstrated that the deficiency of CD38 led to lysosomal lipid accumulation in macrophages, foam cell formation and atherosclerosis, as observed in CD38-/- mice. The present study was designed to examine the effects of niacin on the foam cell formation and explore the underlying mechanisms. Using fluorescent microplate reader and confocal microscope, we found that niacin dose-dependently (in mM: 0, 0.05, 0.1, 0.3, 1 and 2) decreased lysosomal lipid accumulation in bone marrow-derived wild type macrophages treated with oxLDL (40 µg/ml) as stained by lysosomal lipid specific dye of Bodipy 493/503, but it had no effects in CD38-/- macrophages. This niacin-induced lysosomal lipid lowering effects were almost completely abolished by NAADP antagonist of PPADS (100 µM). In the niacin-treated macrophages, the cholesterol level in the purified...

The present study attempted to evaluate whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate lysosome fusion in response to death receptor activation and contribute to membrane raft (MR) clustering and consequent endothelial dysfunction in coronary arterial endothelial cells. By immunohistochemical analysis, vesicle-associated membrane proteins 2 (VAMP-2, vesicle-SNAREs) were found to be abundantly expressed in the endothelium of bovine coronary arteries. Direct lysosome fusion monitoring by N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl]pyridinium dibromide (FM1-43) quenching demonstrated that the inhibition of VAMP-2 with tetanus toxin or specific small interfering ribonucleic acid (siRNA) almost completely blocked lysosome fusion to plasma membrane induced by Fas ligand (FasL), a well-known MR clustering stimulator. The involvement of SNAREs was further confirmed by an increased interaction of VAMP-2 with a target-SNARE protein syntaxin-4 after FasL stimulation in coimmunoprecipitation analysis. Also, the inhibition of VAMP-2 with tetanus toxin or VAMP-2 siRNA abolished FasL-induced MR clustering, its colocalization with a NADPH oxidase unit gp91 phox, and increased superoxide production. Finally, FasL-induced impairment of endothelium-dependent vasodilation was reversed by the treatment of bovine coronary arteries with tetanus toxin or VAMP-2 siRNA. VAMP-2 is critical to lysosome fusion in MR clustering, and this VAMP-2-mediated lysosome-MR signalosomes contribute to redox regulation of coronary endothelial function.

Hypoxia inducible factor (HIF)-1α-mediated gene activation in the renal medulla in response to high salt intake plays an important role in the control of salt sensitivity of blood pressure. High salt-induced activation of HIF-1α in the renal medulla is blunted in Dahl S rats. The present study determined whether the impairment of the renal medullary HIF-1α pathway was responsible for salt sensitive hypertension in Dahl S rats. Renal medullary HIF-1α levels were induced by either transfection of HIF-1α expression plasmid or chronic infusion of CoCl2 into the renal medulla, which was accompanied by increased expressions of anti-hypertensive genes, cyclooxygenase-2 and heme oxygenase-1. Overexpression of HIF-1α transgenes in the renal medulla enhanced the pressure natriuresis, promoted the sodium excretion and reduced sodium retention after salt overload. As a result, hypertension induced by 2-week high salt was significantly attenuated in rats treated with HIF-1α plasmid or CoCl2. These results suggest that an abnormal HIF-1α in the renal medulla may represent a novel mechanism mediating salt-sensitive hypertension in Dahl S rats and that induction of HIF-1α levels in the renal medulla could be a therapeutic approach for the treatment of salt-sensitive hypertension.

Objective: To investigate the mechanism of Astragalus-Angelica Mixture (AAM) ’s effects on lipid metabolism disturbance in nephrotic rats.Methods: To examine the effects of AAM on serum albumin, lipid levels, and activities of lipoprotein lipase (LPL) and lecithin-cholesterol acyltransferase (LCAT), which are key enzymes for metabolism of lipid in immune-induced nephrotic hyperlipidemia rats and exogenous hyperlipidemia rats.Results: In nephrotic rats, serum albumin was reduced, lipid increased significantly, LPL activity decreased markedly and the LCAT activity was relatively insufficient. Activities of LPL and LCAT increased obviously in AAM treated nephrotic rats. There were no change of activities of LPL and LCAT in exogenous hyperlipidemia rats and AAM showed no effect on the activities of these two enzymes.Conclusion: The effect of AAM on regulating lipid metabolism might be due to enhance the clearance of both triglyceride-rich and cholesterol-rich apoB containing lipoprotein by improving the activities of LPL and LCAT.

This study explored the mechanism mediating the aggregation of membrane NADPH oxidase (NOX) subunits and subsequent activation of this enzyme in bovine coronary arterial endothelial cells (CAECs). With confocal microscopy, we found that FasL stimulated lipid rafts (LRs) clustering with NOX subunit aggregation and acid sphingomyelinase (ASM) gathering, which was blocked by the siRNA of sortilin, an intracellular protein responsible for the binding and targeting of ASM to lysosomes. Correspondingly, FasL-induced O2·− production through NOX in LRs fractions was abolished by sortilin siRNA. Further, with flow-cytometry and fluorescence resonance energy transfer (FRET) analysis, we surprisingly demonstrated that after FasL stimulation, sortilin was exposed to cell membranes from lysosomes together with Lamp-1 and ASM, and these lysosomal components were aggregated and form a signaling complex in cell membranes. With co-immunoprecipitation, lysosomal sortilin and ASM were found to interact more strongly when CAECs were stimulated by FasL. Functionally, inhibition of either sortilin expression, lysosome function, LRs clustering, or NOX activity significantly attenuated FasL-induced decrease in nitric oxide (NO) levels. It is concluded that lysosome-targeted ASM, through sortilin, is able to traffic to and expose to cell-membrane surface, which may lead to LRs clustering and NOX activation in CAECs. Antioxid. Redox Signal. 12, 703–712.