New Zealand White rabbits were used to investigate the influence of increasing dietary P concentrations on growth performance, mineral balance, kidney calcification and bone development. The minimum dietary P requirement of 0·22 % (National Research Council) is usually exceeded in commercial natural-ingredient chows, leading to undesirable kidney calcifications. In order to study the optimal dietary P level, rabbits were fed semi-purified diets with four different P levels (0·1, 0·2, 0·4, and 0·8 %; w/w) at a constant dietary Ca concentration (0·5 %) during an 8-week period. Body weight and growth were not influenced by the dietary P level. During two periods (days 20 -23 and 48 -51), faeces and urine were collected quantitatively for the analysis of Ca, Mg and P and balances were calculated. Increased dietary P intake caused increased urinary and faecal P excretion and P apparent absorption and retention. Faecal Ca excretion increased with higher dietary P levels, whereas urinary Ca excretion reacted inversely. The apparent absorption of Ca became reduced at higher dietary P concentrations, but Ca retention was unchanged. The response of Mg was in a similar direction to that of the Ca balance. Kidney mineral content increased with higher dietary P levels, indicating the presence of calcified deposits. Nephrocalcinosis became more severe in kidney cortex and medulla at increasing dietary P levels, as was confirmed by histological analysis. Femur bone length was not differentially influenced by dietary P. Bone density (g/cm 3 ) of the femur diaphysis became significantly lower at the 0·8 % dietary P level as compared with the 0·2 % P group only. The bone Mg content was significantly increased on the 0·8 % P diet, both in the diaphysis and epiphysis. Plasma P concentration increased and plasma Ca decreased with higher dietary P levels, whereas plasma Mg levels were unaffected. The present study shows that the current recommended minimum dietary P level of 0·2 % for rabbits, as advised by the National Research Council in 1977, leads to a normal growth and bone development, but also causes some degree of kidney calcifications at a dietary Ca level of 0·5 %. As the dietary P level of 0·1 % virtually prevented kidney calcification and at the same time did not give evidence for any deleterious effects on growth and bone development, this indicates that the current recommended dietary P level for rabbits should be regarded as a maximum advisable concentration, and that a lower P level may be more optimal.

Guanine quadruplexes (G4s) are important targets for cancer treatments as their stabilization has been associated with a reduction of telomere ends or a lower oncogene expression. Although less abundant than purely organic ligands, metal complexes have shown remarkable abilities to stabilize G4s, and a wide variety of techniques have been used to characterize the interaction between ligands and G4s. However, improper alignment between the large variety of experimental techniques and biological activities can lead to improper identification of top candidates, which hampers progress of this important class of G4 stabilizers. To address this, we first review the different techniques for their strengths and weaknesses to determine the interaction of the complexes with G4s, and provide a checklist to guide future developments towards comparable data. Then, we surveyed 74 metal-based ligands for G4s that have been characterized to the in vitro level. Of these complexes, we assessed which methods were used to characterize their G4-stabilizing capacity, their selectivity for G4s over double-stranded DNA (dsDNA), and how this correlated to bioactivity data. For the biological activity data, we compared activities of the G4-stabilizing metal complexes with that of cisplatin. Lastly, we formulated guidelines for future studies on G4-stabilizing metal complexes to further enable maturation of this field. Graphical abstract

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