BackgroundStudies have reported “dysbiotic” changes to gut microbiota, such as depletion of gut bacteria that produce short-chain fatty acids (SCFAs) through gut fermentation of fiber, in CKD and diabetes. Dietary fiber is associated with decreased inflammation and mortality in CKD, and SCFAs have been proposed to mediate this effect.MethodsTo explore dietary fiber’s effect on development of experimental diabetic nephropathy, we used streptozotocin to induce diabetes in wild-type C57BL/6 and knockout mice lacking the genes encoding G protein–coupled receptors GPR43 or GPR109A. Diabetic mice were randomized to high-fiber, normal chow, or zero-fiber diets, or SCFAs in drinking water. We used proton nuclear magnetic resonance spectroscopy for metabolic profiling and 16S ribosomal RNA sequencing to assess the gut microbiome.ResultsDiabetic mice fed a high-fiber diet were significantly less likely to develop diabetic nephropathy, exhibiting less albuminuria, glomerular hypertrophy, podocyte injury, and interstitial fibrosis compared with diabetic controls fed normal chow or a zero-fiber diet. Fiber beneficially reshaped gut microbial ecology and improved dysbiosis, promoting expansion of SCFA-producing bacteria of the genera Prevotella and Bifidobacterium, which increased fecal and systemic SCFA concentrations. Fiber reduced expression of genes encoding inflammatory cytokines, chemokines, and fibrosis-promoting proteins in diabetic kidneys. SCFA-treated diabetic mice were protected from nephropathy, but not in the absence of GPR43 or GPR109A. In vitro, SCFAs modulated inflammation in renal tubular cells and podocytes under hyperglycemic conditions.ConclusionsDietary fiber protects against diabetic nephropathy through modulation of the gut microbiota, enrichment of SCFA-producing bacteria, and increased SCFA production. GPR43 and GPR109A are critical to SCFA-mediated protection against this condition. Interventions targeting the gut microbiota warrant further investigation as a novel renoprotective therapy in diabetic nephropathy.
Oxygen adatom, charge state, noncontact atomic force microscopy (nc-AFM), Kelvin probe force microscopy (KPFM), tipsample distance, tip-induced electric field, density functional theory (DFT).
A surface potential measurement method using amplitude-modulation and heterodyne techniques is proposed. The effect of the stray capacitance between a cantilever and a sample in Kelvin probe force microscopy and the electrostatic force spectroscopy measurements are almost completely removed, because the distance (z) dependence of the modulated electrostatic force increases from 1/z to1/z2. This method improves the sensitivity of short range forces and reduces the surface potential measurement crosstalk that is induced by topographic feedback. This method has the advantage of high potential sensitivity due to the high cantilever Q value under vacuum. Quantitative surface potential measurements are demonstrated.
Abstract:The influence of microchemistry on the softening behaviour of two cold-rolled AlMn-Fe-Si alloys with different initial amounts of Mn (0.4 and 1.0 wt%, respectively) is studied.In addition to their as-cast conditions, the supersaturated Al-Mn-Fe-Si alloys were appropriately homogenized at two different conditions, which together produce three different states of microchemistry for each alloy, i.e. solutes and second-phase particles. Samples with different microchemistry states were then cold-rolled before subsequent back-annealing at different temperatures for the two alloys. The softening and concurrent precipitation behaviours of the samples have been monitored by hardness and electrical conductivity measurements respectively, and the final microstructure in terms of grain structure and texture has been characterized by EBSD. It is clearly demonstrated that the amount of Mn and the actual microchemistry state as determined by the homogenization procedure strongly influence the softening behaviour. Both a fine dispersion of pre-existing dispersoids and strong concurrent precipitation may slow down the recrystallization kinetics considerably and give a very coarse grain structure and textures commonly associated with dispersoids effects, although some are slightly atypical.2
We
study a low-temperature on-surface reversible chemical reaction
of oxygen atoms to molecules in ultrahigh vacuum on the semiconducting
rutile TiO2(110)-(1 × 1) surface. The reaction is
activated by charge transfer from two sources, natural surface/subsurface
polarons and experimental Kelvin probe force spectroscopy as a tool
for electronic charge manipulation with single electron precision.
We demonstrate a complete control over the oxygen species not attainable
previously, allowing us to deliberately discriminate in favor of charge
or bond manipulation, using either direct charge injection/removal
through the tip-oxygen adatom junction or indirectly via polarons. Comparing our ab initio calculations
with experiment, we speculate that we may have also manipulated the
spin on the oxygens, allowing us to deal with the singlet/triplet
complexities associated with the oxygen molecule formation. We show
that the manipulation outcome is fully governed by three experimental
parameters, vertical and lateral tip positions and the bias voltage.
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