The kidney was recognized as a dominant organ for uric acid excretion. The main aim of the study demonstrated intestinal tract was an even more important organ for serum uric acid (SUA) lowering. Sprague-Dawley rats were treated normally or with antibiotics, uric acid, adenine, or inosine of the same molar dose orally or intraperitoneally for 5 days. Rat’s intestinal tract was equally divided into 20 segments except the cecum. Uric acid in serum and intestinal segment juice was assayed. Total RNA in the initial intestinal tract and at the end ileum was extracted and sequenced. Protein expression of xanthine dehydrogenase (XDH) and urate oxidase (UOX) was tested by Western blot analysis. The effect of oral UOX in lowering SUA was investigated in model rats treated with adenine and an inhibitor of uric oxidase for 5 days. SUA in the normal rats was 20.93±6.98 μg/ml, and total uric acid in the intestinal juice was 308.27±16.37 μg, which is two times more than the total SUA. The uric acid was very low in stomach juice, and attained maximum in the juice of the first segment (duodenum) and then declined all the way till the intestinal end. The level of uric acid in the initial intestinal tissue was very high, where XDH and most of the proteins associated with bicarbonate secretion were up-regulated. In addition, SUA was decreased by oral UOX in model rats. The results suggested that intestinal juice was an important pool for uric acid, and intestinal tract was an important organ for SUA lowering. The uric acid distribution was associated with uric acid synthesis and secretion in the upper intestinal tract, and reclamation in the lower.

The main aim of the present study was to investigate the biological function of uric acid. The level of uric acid in different organs in normal male rats was determined with uric acid assay kits, and the expression level of genes in the organs was determined by RNA quantitative sequencing. The correlation analysis between uric acid in the organs and gene expression (measured by FPKM value) was made. Serum uric acid (SUA) in patients with breast cancer or with breast benign tumor was assayed when the diagnosis was made, and SUA in patients with breast cancer was also assayed just after chemotherapy. There were 1937 mRNAs whose expression level significantly correlated with the level of uric acid, and most of which were associated with purine or nucleoside metabolism, cellular metabolism, cell cycles, and cell death pathways. Further analysis showed that the level of uric acid was highly correlated with cell death rather than cell viability. The level of SUA in patients with breast cancer was higher than that in patients with breast benign tumor, and the SUA increased after chemotherapy. All the results suggested that uric acid was mainly synthesized from local nucleosides degraded from dead cells, and uric acid could be an important biomarker for cell death rather than an antioxidant for neural protection.

Candida albicans is a ubiquitous clinical fungal pathogen. Prolonged use of the first-line antifungal agent fluconazole (FLC) has intensified fungal resistance and limited its effectiveness for the treatment of fungal infections. The combined administration of drugs has been extensively studied and applied. SWL-1 is a lignin compound derived from the Traditional Chinese Medicine Schisandra chinensis. In this study, we show that SWL-1 reverses resistance to fluconazole in C. albicans when delivered in combination, with a sharp decrease in the IC 50 of fluconazole from >200 to 3.74 ± 0.25 μg/ml, and also reverses the fluconazole resistance of C. albicans in vitro, with IC 50 from >200 to 5.3 ± 0.3 μg/ml. Moreover, killing kinetics curves confirmed the synergistic effects of fluconazole and SWL-1. Intriguingly, when SWL-1 was administered in combination with fluconazole in a mouse model of systemic infection, the mortality of mice was markedly decreased and fungal colonization of the kidney and lung was reduced. Further mechanistic studies showed that SWL-1 significantly decreased intracellular adenosine 5'-triphosphate (ATP) levels and inhibited the function of the efflux pump responsible for fluconazole resistance of C. albicans. Proteomic analysis of the effects of SWL-1 on C. albicans showed that several enzymes were downregulated in the glycolytic pathway. We speculate that SWL-1 significantly decreased intracellular ATP levels by hindering the glycolysis, and the function of the efflux pump responsible for fluconazole resistance of C. albicans was inhibited, resulting in restoration of fluconazole sensitivity in FLC-resistant C. albicans. This study clarified the effects and mechanism of SWL-1 on C. albicans in vitro and in vivo, providing a novel approach to overcoming fungal resistance.

It was generally expected that monotone schemes are oscillationfree for hyperbolic conservation laws. However, recently local oscillations were observed and usually understood to be caused by relative phase errors. In order to further explain this, we first investigate the discretization of initial data that trigger the chequerboard mode, the highest frequency mode. Then we proceed to use the discrete Fourier analysis and the modified equation analysis to distinguish the dissipative and dispersive effects of numerical schemes for low frequency and high frequency modes, respectively. It is shown that the relative phase error is of order O(1) for the high frequency modes u n j = λ n k e iξj , ξ ≈ π, but of order O(ξ 2 ) for low frequency modes (ξ ≈ 0). In order to avoid numerical oscillations, the relative phase errors should be offset by numerical dissipation of at least the same order. Numerical damping, i.e. the zero order term in the corresponding modified equation, is important to dissipate the oscillations caused by the relative phase errors of high frequency modes. This is in contrast to the role of numerical viscosity, the second order term, which is the lowest order term usually present to suppress the relative phase errors of low frequency modes.