UCS1025A is a fungal polyketide/alkaloid that displays strong inhibition of telomerase. The structures of UCS1025A and related natural products are featured by a tricyclic furopyrrolizidine connected to a trans-decalin fragment. We mined the genome of a thermophilic fungus and activated the ucs gene cluster to produce UCS1025A at a high titer. Genetic and biochemical analysis revealed a PKS-NRPS assembly line that activates 2S,3S-methylproline derived from l-isoleucine, followed by Knoevenagel condensation to construct the pyrrolizidine moiety. Oxidation of the 3S-methyl group to a carboxylate leads to an oxa-Michael cyclization and furnishes the furopyrrolizidine. Our work reveals a new strategy used by nature to construct heterocyclic alkaloid-like ring systems using assembly line logic.

MDCTV provided a new possible way to assess dysfunction of tunneled hemodialysis central venous catheters.

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Introduction. Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decrease graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-αKlotho axis and cardiovascular complications after transplantation. Materials and Methods. 209 kidney transplant recipients were included and further divided into treated and untreated groups depending on whether receiving vitamin D supplementation. We tracked the state of THPT, bone metabolism, FGF23-αKlotho axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, αKlotho levels, THPT and cardiovascular complications in recipients. Results. Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in treated group comparing with untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for iFGF23 and αKlotho levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12. Conclusion. Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.

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