Extrarenal phenotypes of the UT-B knockout mouse.

The urea transporter UT-B is expressed in multiple tissues including erythrocytes, kidney, brain, heart, liver, colon, bone marrow, spleen, lung, skeletal muscle, bladder, prostate, and testis in mammals. Phenotype analysis of UT-B-null mice has confirmed that UT-B deletion results in a urea-selective urine-concentrating defect (see Chap. 9 ). The functional significance of UT-B in extrarenal tissues studied in the UT-B-null mouse is discussed in this chapter. UT-B-null mice present depression-like behavior with urea accumulation and nitric oxide reduction in the hippocampus. UT-B deletion causes a cardiac conduction defect, and TNNT2 and ANP expression changes in the aged UT-B-null heart. UT-B also plays a very important role in protecting bladder urothelium from DNA damage and apoptosis by regulating the urea concentration in urothelial cells. UT-B functional deficiency results in urea accumulation in the testis and early maturation of the male reproductive system. These results show that UT-B is an indispensable transporter involved in maintaining physiological functions in different tissues.

A novel small-molecule thienoquinolin urea transporter inhibitor acts as a potential diuretic.

Urea transporters (UTs) are a family of membrane channel proteins that are specifically permeable to urea and play an important role in intrarenal urea recycling and in urine concentration. Using an erythrocyte osmotic lysis assay, we screened a small-molecule library for inhibitors of UT-facilitated urea transport. A novel class of thienoquinolin UT-B inhibitors were identified, of which PU-14 had potent inhibition activity on human, rabbit, rat, and mouse UT-B. The half-maximal inhibitory concentration of PU-14 on rat UT-B-mediated urea transport was ∼0.8 µmol/l, and it did not affect urea transport in mouse erythrocytes lacking UT-B but inhibited UT-A-type urea transporters, with 36% inhibition at 4 µmol/l. PU-14 showed no significant cellular toxicity at concentrations up to its solubility limit of 80 µmol/l. Subcutaneous delivery of PU-14 (at 12.5, 50, and 100 mg/kg) to rats caused an increase of urine output and a decrease of the urine urea concentration and subsequent osmolality without electrolyte disturbances and liver or renal damages. This suggests that PU-14 has a diuretic effect by urea-selective diuresis. Thus, PU-14 or its analogs might be developed as a new diuretic to increase renal fluid clearance in diseases associated with water retention without causing electrolyte imbalance. PU-14 may establish 'chemical knockout' animal models to study the physiological functions of UTs.

Machine learning prediction of pyrolytic products of lignocellulosic biomass based on physicochemical characteristics and pyrolysis conditions.

This study predicts pyrolytic product yields via machine learning algorithms from biomass physicochemical characteristics and pyrolysis conditions. Random forest (RF), gradient boosting decision tree (GBDT), eXtreme Gradient Boosting (XGBoost), and Adaptive Boost (Adaboost) algorithms are comparatively analyzed. Among these algorithms, the RF algorithm is the best modeling algorithm and performs best in predicting the bio-oil yield and performs well in predicting biochar and pyrolytic gas yields. The moisture content, carbon content, and final heating temperature are the most important factors in predicting pyrolysis product yields, and biomass characteristics are more important than pyrolysis conditions. Furthermore, the carbon content positively affects the bio-oil yield and negatively affects the biochar yield, and the final temperature positively affects the pyrolytic gas yield and negatively affects the biochar yield. This work provides new insight for controlling the yields of pyrolytic products via the RF algorithm, which can facilitate the process optimization in engineering applications.

Urea transporter UT-B deletion induces DNA damage and apoptosis in mouse bladder urothelium.

BACKGROUND: Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. METHODOLOGY/PRINCIPAL FINDINGS: Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. CONCLUSIONS/SIGNIFICANCE: UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.