Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii.

Ribose-5-phosphate (R5P) is a precursor for nucleic acid biogenesis; however, the importance and homeostasis of R5P in the intracellular parasite Toxoplasma gondii remain enigmatic. Here, we show that the cytoplasmic sedoheptulose-1,7-bisphosphatase (SBPase) is dispensable. Still, its co-deletion with transaldolase (TAL) impairs the double mutant's growth and increases 13C-glucose-derived flux into pentose sugars via the transketolase (TKT) enzyme. Deletion of the latter protein affects the parasite's fitness but is not lethal and is correlated with an increased carbon flux via the oxidative pentose phosphate pathway. Further, loss of TKT leads to a decline in 13C incorporation into glycolysis and the TCA cycle, resulting in a decrease in ATP levels and the inability of phosphoribosyl-pyrophosphate synthetase (PRPS) to convert R5P into 5'-phosphoribosyl-pyrophosphate and thereby contribute to the production of AMP and IMP. Likewise, PRPS is essential for the lytic cycle. Not least, we show that RuPE-mediated metabolic compensation is imperative for the survival of the ΔsbpaseΔtal strain. In conclusion, we demonstrate that multiple routes can flexibly supply R5P to enable parasite growth and identify catalysis by TKT and PRPS as critical enzymatic steps. Our work provides novel biological and therapeutic insights into the network design principles of intracellular parasitism in a clinically-relevant pathogen.

Reversal of cardiac and renal damage in a teenager with hypertension: A case report.

The authors describe the case of a 16-year-old male who was incidentally found to have a blood pressure of 200/? mmHg 6 months previously due to blurred vision and was diagnosed with "high risk of hypertension grade 3, renal insufficiency, hypertensive encephalopathy, hypertensive heart disease, and fundus hemorrhage" after relevant examinations were performed. His blood pressure fluctuated around 120/90 mmHg after beginning antihypertensive treatment. While the diagnostic work-up of his hypertension was inconclusive, he had severe hypertension with brachydactyly type E and short stature on physical examination. The patient's cardiac damage and renal insufficiency ultimately returned to normal after strict blood pressure control, suggesting that hypertension and brachydactyly syndrome alone do not cause cardiac and renal damage.

Breast intervention device for low-field MRI with a customized unilateral coil.

With the incidence of breast cancer rising to the top among female malignant tumors, magnetic resonance images guided breast biopsy intervention and minimally invasive treatment have developed as a clinically practical research issue. High field studies have shown the diagnostic value of breast MRI, but the examination costs greatly exceed those of competing conventional mammography. In this case, low-field MRI cannot merely provide typical MRI contrast, but also significantly reduce the cost of diagnosis and treatment for breast cancer patients. This work describes a unilateral breast coil and prototype intervention device, which provides a customized solution for low-field MRI-guided breast intervention. Results demonstrate that the low-field MRI breast intervention device facilitates medical intervention procedures. And the designed positioning device can locate the target lesion within 2-3 mm accuracy. Phantom tests with the customized unilateral coil indicate that the open loops perform as well as the 4-channel commercial closed breast coil, presenting a relatively good SNR (signal-to-noise ratio) and uniformity characteristics. MR scanning images of the volunteer breast using the breast intervention coil also show high SNR, which lays a foundation for further implementation of image-guided breast interventional minimally invasive surgery with the low-field MRI system.

Development of a novel MR-conditional microwave needle for MR-guided interventional microwave ablation at 1.5T.

PURPOSE: To develop an MR-conditional microwave needle that generates a spherical ablation zone and clear MRI visibility for MR-guided microwave ablation. METHODS: An MR-conditional microwave needle consisting of zirconia tip and TA18 titanium alloy tube was investigated. The numerical model was created to optimize the needle's geometry and analyze its performance. A geometrically optimized needle was produced using non-magnetic materials based on the electromagnetics simulation results. The needle's mechanical properties were tested per the Chinese pharmaceutical industry standard YY0899-2013. The MRI visibility performance and ablation characteristics of the needle was tested both in vitro (phantom) and in vivo (rabbit) at 1.5T. The RF-induced heating was evaluated in ex vivo porcine liver. RESULTS: The needle's mechanical properties met the specified requirements. The needle susceptibility artifact was clearly visible both in vitro and in vivo. The needle artifact diameter (A) was small in in vivo (Ashaft: 4.96 ± 0.18 mm for T1W-FLASH, 3.13 ± 0.05 mm for T2-weighted fast spin-echo (T2W-FSE); Atip: 2.31 ± 0.09 mm for T1W-FLASH, 2.29 ± 0.08 mm for T2W-FSE; tip location error [TLE]: -0.94 ± 0.07 mm for T1W-FLASH, -1.10 ± 0.09 mm for T2W-FSE). Ablation zones generated by the needle were nearly spherical with an elliptical aspect ratio ranging from 0.79 to 0.90 at 30 W, 50 W for 3, 5, 10 min duration ex vivo ablations and 0.86 at 30 W for 10 min duration in vivo ablations. CONCLUSION: The designed MR-conditional microwave needle offers excellent mechanical properties, reliable MRI visibility, insignificant RF-induced heating, and a sufficiently spherical ablation zone. Further clinical development of MR-guided microwave ablation appears warranted.