Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

Hypertension in patients with chronic kidney disease (CKD) strongly associates with cardiovascular events. Among patients with CKD, reducing the accumulation of uremic toxins may protect against the development of hypertension and progression of renal damage, but there are no established therapies to accomplish this. Here, overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly, and inflammation in the setting of renal failure. In addition, SLCO4C1 overexpression decreased plasma levels of the uremic toxins guanidino succinate, asymmetric dimethylarginine, and the newly identified trans-aconitate. We found that xenobiotic responsive element core motifs regulate SLCO4C1 transcription, and various statins, which act as inducers of nuclear aryl hydrocarbon receptors, upregulate SLCO4C1 transcription. Pravastatin, which is cardioprotective, increased the clearance of asymmetric dimethylarginine and trans-aconitate in renal failure. These data suggest that drugs that upregulate SLCO4C1 may have therapeutic potential for patients with CKD.

Interest has recently been shown again in colistin because of the increased prevalence of infections caused by multidrug-resistant Gram-negative bacteria. Although the potential for nephrotoxicity is a major dose-limiting factor in colistin use, little is known about the mechanisms that underlie colistin-induced nephrotoxicity. In this study, we focused on an endocytosis receptor, megalin, that is expressed in renal proximal tubules, with the aim of clarifying the role of megalin in the kidney accumulation and nephrotoxicity of colistin. We examined the binding of colistin to megalin by using a vesicle assay. The kidney accumulation, urinary excretion, and concentrations in plasma of colistin in megalin-shedding rats were also evaluated. Furthermore, we examined the effect of megalin ligands and a microtubule-depolymerizing agent on colistin-induced nephrotoxicity. We found that cytochrome c, a typical megalin ligand, inhibited the binding of colistin to megalin competitively. In megalin-shedding rats, renal proximal tubule colistin accumulation was decreased (13.5 ؎ 1.6 and 21.3 ؎ 2.6 g in megalin-shedding and control rats, respectively). Coadministration of colistin and cytochrome c or albumin fragments resulted in a significant decrease in urinary N-acetyl-␤-D-glucosaminidase (NAG) excretion, a marker of renal tubular damage (717.1 ؎ 183.9 mU/day for colistin alone, 500.8 ؎ 102.4 mU/day for cytochrome c with colistin, and 406.7 ؎ 156.7 mU/day for albumin fragments with colistin). Moreover, coadministration of colistin and colchicine, a microtubule-depolymerizing agent, resulted in a significant decrease in urinary NAG excretion. In conclusion, our results indicate that colistin acts as a megalin ligand and that megalin plays a key role in the accumulation in the kidney and nephrotoxicity of colistin. Megalin ligands may be new targets for the prevention of colistininduced nephrotoxicity.

The relationship between the imide structures and morphology are discussed in order to develop heat resistant polyimides having excellent processability and toughness. Addition-type imide oligomers consisting of asymmetric 2,3,3 ,4 -biphenyltetracarboxylic dianhydride (a-BPDA) and 3,4 -oxydianiline (3,4 -ODA) and/or 4,4 -oxydianiline (4,4 -ODA) with 4-phenylethynyl phthalic anhydride (PEPA) were synthesized and characterized. The imide oligomers derived from 3,4 -ODA; 4,4 -ODA (50:50) comonomer having molecular weights of 5240 g mol −1 (Oligo-10) and 1340 g mol −1 (Oligo-1.5) showed good solubility in aprotic solvents such as DMAc and NMP, and were successfully cured at 370 • C for one hour. The thermal curing process, and thermal and rheological properties of the imide oligomers were investigated by FT-IR, differential scanning calorimetry, thermogravimetric analysis, and dynamic rheometry. It was observed that the melt flow dramatically decreased above the T g for Oligo-1.5, resulting in a viscosity as low as 200 Poise at 300 • C. Whereas, a melt viscosity for Oligo-10 was 20 000 Poise at 365 • C. The glass transition temperatures of these cured oligomers were 341 • C and 308 • C, respectively. In addition to the excellent melt property, the cured oligomers exhibited good thermo-oxidative stability. Furthermore, the cured imide oligomer consisting of a-BPDA and 4,4 -ODA with PEPA (Oligo-4.5) exhibited over 13% flexural elongation and a T g of 343 • C. Their T-300 carbon fibre composites were also well consolidated demonstrating excellent processability and properties. It is concluded that amorphous, aromatic imide structures without any weak linkages

This paper presents a novel feedback-control law for coordinating the motion of multiple holonomic mobile robots to capture/enclose a target by making troop formations. This motion coordination is a cooperative behavior for security against invaders in surveillance areas. Each robot in this control law has its own coordinate system and it senses a target/invader, other robots and obstacles, to achieve this cooperative behavior without making any collision. Although there is no centralized controller and each robot has local feedback that is relative-position feedback, all the robots are asymptotically stabilized, and they make formations enclosing a target. Each robot especially has a vector referred to as a "formation vector," and the formations are controllable by the vectors. As for determining the formation vectors, we use a reactive-control framework in which robots have some reactions heuristically designed according to this cooperative behavior. Therefore, this robotic system is a hybrid system that consists of a feedback-control law and a reactive-control framework. The validity of this hybrid system is supported by computer simulations.

This study aimed to investigate the shear bond strength of an autopolymerizing resin to a nylon denture base polymer (Lucitone FRS: LT) subjected to different surface treatments, and the results thereof compared with a heat-polymerizing resin and a polycarbonate polymer. Specimens were divided into five groups according to the surface treatment method: polishing (#600), sandblasting, adhesive primer application (resin primer), sandblasting + adhesive primer application, and tribochemical coating (Rocatec system). Following which, specimens were subjected to a shear bond strength test and Si concentrations were measured using an electron probe microanalyzer (EPMA). On shear bond strength, that of LT with tribochemical coating was significantly higher than the other groups. On EPMA results, the surface of LT with tribochemical coating was found to be covered with a silica film. Therefore, findings in this study indicated that silica-coating by Rocatec system was effective in improving the bond strength of nylon denture base polymer to autopolymerizing repair resin.

Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroidresistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin-induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I-IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.

The purpose of our study was to evaluate the effects of surface modifications on the bond strength between veneering porcelains and Yttria-stabilized tetragonal zirconia (Y-TZP). In a bond strength tests, the effect of control, 70 µm alumina-sandblasting, 30 µm and 110 µm silica-coating of the Y-TZP surface on bonding were evaluated with veneering porcelains. In addition, the effect of surface modification on the flexural strength of Y-TZP was also evaluated. The data was analyzed using one-way ANOVA and Tukey test. All specimens showed bond strength values in excess of 25 MPa, the minimum allowed by ISO9693. In addition, significantly differences were found between the control and the 30 µm silica-coated. On the other hand the flexural strength of Y-TZP does not significantly difference for any surface modification. These results indicate that silica-coating may provide an effective pre-treatment for this enhancement of the bond strength while maintaining the strength of Y-TZP.