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.