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p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 8.0px Helvetica; color: #2f2a2b} span.s1 {font: 5.5px Helvetica} Na1/H1 exchanger (NHE1) activation is required for multiple microglial functions. We investigated effects of selective deletion of microglial Nhe1 in Cx3cr1-CreER;Nhe1f/f mice on neuroinflammation and tissue repair after ischemic stroke. Infarct volume was similar in corn oil or tamoxifen (Tam)- treated mice at 48 hr and 14 days post-stroke. However, the Tam-treated mice showed significantly higher survival rate and faster neurological function recovery during day 1–14 post-stroke. Deletion of microglial Nhe1 prevented the elevation of CD11b1/CD45low-med microglia in the ischemic hemisphere at day 3 post-stroke, but stimulated expression of Ym1, CD68, TGF-b, IL-10, decreased expression of CD86 and IL-1b, and reduced GFAP1 reactive astrocytes. Moreover, at day 14 post-stroke, enhanced white matter myelination was detected in the microglial Nhe1 deleted mice. In comparison, neuronal Nhe1-null mice (the CamKII-Cre1/2;Nhe1f/f mice) showed a significant reduction in both acute and subacute infarct volume, along with increased survival rate and moderate neurological function recovery. However, these neuronal Nhe1-null mice did not exhibit reduced activation of CD11b1/CD45low-med microglia or CD11b1/CD45hi macrophages in the ischemic brains, and they exhibited no reductions in white matter lesions. Taken together, this study demonstrated that deletion of microglial and neuronal Nhe1 had differential effects on ischemic brain damage. Microglial NHE1 is involved in pro-inflammatory responses during post-stroke brain tissue repair. In contrast, neuronal NHE1 activation is directly associated with the acute ischemic neuronal injury but not inflammation. Our study reveals that NHE1 protein is a potential therapeutic target critical for differential regulation of ischemic neuronal injury, demyelination and tissue repair.

Stimulation of Na+/H+ exchanger isoform 1 (NHE1) in astrocytes causes ionic dysregulation under ischemic conditions. In this study, we created a Nhe1flox/flox (Nhe1f/f) mouse line with exon 5 of Nhe1 flanked with two loxP sites and selective ablation of Nhe1 in astrocytes was achieved by crossing Nhe1f/f mice with Gfap-CreERT2 Cre-recombinase mice. Gfap-CreERT2+/−;Nhe1f/f mice at postnatal day 60–90 were treated with either corn oil or tamoxifen (Tam, 75 mg/kg/day, i.p.) for 5 days. After 30 days post-injection, mice underwent transient middle cerebral artery occlusion (tMCAO) to induce ischemic stroke. Compared with the oil-vehicle group (control), Tam-treated Gfap-CreERT2+/−;Nhe1f/f (Nhe1 KO) mice developed significantly smaller ischemic infarction, less edema, and less neurological function deficits at 1–5 days after tMCAO. Immunocytochemical analysis revealed less astrocytic proliferation, less cellular hypertrophy, and less peri-lesion gliosis in Nhe1 KO mouse brains. Selective deletion of Nhe1 in astrocytes also reduced cerebral microvessel damage and blood–brain barrier (BBB) injury in ischemic brains. The BBB microvessels of the control brains show swollen endothelial cells, opened tight junctions, increased expression of proinflammatory protease MMP-9, and significant loss of tight junction protein occludin. In contrast, the Nhe1 KO mice exhibited reduced BBB breakdown and normal tight junction structure, with increased expression of occludin and reduced MMP-9. Most importantly, deletion of astrocytic Nhe1 gene significantly increased regional cerebral blood flow in the ischemic hemisphere at 24 hr post-MCAO. Taken together, our study provides the first line of evidence for a causative role of astrocytic NHE1 protein in reactive astrogliosis and ischemic neurovascular damage.

Water status and N fertility are the critical factors in micronutrient accumulation in grain of wheat (Triticum aestivum L.). This field experiment was conducted to examine whether the changes in N fertility and water management can influence micronutrient concentration and bioavailability in wheat grown in soils with existing low micronutrient concentrations within drought-prone regions. The results indicate that fertilizer N (120 or 240 kg N ha–¹) application significantly improved grain Zn, Fe, Cu, and protein concentration with a mean increase of 24.7, 39.2, 18.6, 23.9% in 2009/2010 and 8.9, 21.1, 10.5, 29.6% in 2010/2011, respectively, when compared with the unfertilized treatment. However, grain Mn concentration in both cropping seasons were significantly decreased (on average by 8.4%) by N fertilization. Compared to the no irrigation treatment (NI), the water-saving treatment (RF) significantly increased grain Zn by an average of 13.2%, grain Fe by 22.2%, grain Mn by 4.4%, and grain protein by 8.3%. Grain phytic acid (PA) concentration and PA/micronutrient ratios were on average 28.0 and 32.2% lower in the N fertilized treatment than in the unfertilized treatment. Decreasing the N application rate from 240 to 120 kg N ha–¹ did not affect much of the grain nutritional quality, with the exception of a significant decrease in grain Zn concentration, and a significant increase in grain PA concentrations and the PA/Zn molar ratio. These data demonstrate the importance of monitoring grain Zn concentrations, and perhaps the inclusion of supplemental Zn when adopting alternative N fertilizer management regimes in northern China.

Two hybrid coatings synthesized by using alkoxysilanes as precursors in a sol–gel process, differing from each other in terms of the organic components in alkoxysilanes, have been developed to improve the water repellent properties of base paper. The sol–gel-coated base paper samples were characterized by scanning electron microscopy, atomic force microscopy, confocal laser scanning microscopy, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and contact angle measurements. The sol–gel coatings were found to clearly change the surface properties of base paper. Thin coating layers were formed on base paper surfaces. The topographical data indicated the formation of discontinuous thin films; the time-of-flight secondary ion mass spectrometry analyses confirmed that the coatings were covering the fibres but only partially covered the fibre–fibre intersections. Water and the subsequent heat treatment used as a reference treatment reduced the surface roughness and porosity and slightly changed the surface chemistry of the base paper. The wettability and absorptivity of base paper was clearly reduced by the applied coatings. Copyright © 2011 John Wiley & Sons, Ltd.