CE-IOUS using sonazoid can allow surgeons to investigate the whole liver with enough time and to find new metastases intraoperatively.

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a b s t r a c tBiocompatible hybrid particles composed of hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , HAp) and ferrite (g-Fe 2 O 3 and Fe 3 O 4 ) were synthesized using a two-step procedure. First, the ferrite particles were synthesized by co-precipitation. Second, the suspension, which was composed of ferrite particles by a co-precipitation method, Ca(NO 3 ) 2 , and H 3 PO 4 aqueous solution with surfactant, was nebulized into mist ultrasonically. Then the mist was pyrolyzed at 1000 1C to synthesize HAp-ferrite hybrid particles. The molar ratio of Fe ion and HAp was (Fe 2 + and Fe 3 + )/HAp ¼6. The synthesized hybrid particle was round and dimpled, and the average diameter of a secondary particle was 740 nm. The cross section of the synthesized hybrid particles revealed two phases: HAp and ferrite. The ferrite was coated with HAp. The synthesized hybrid particles show a saturation magnetization of 11.8 emu/g. The net saturation magnetization of the ferrite component was calculated as 32.5 emu/g. The temperature increase in the AC-magnetic field (370 kHz, 1.77 kA/m) was 9 1C with 3.4 g (the ferrite component was 1.0 g). These results show that synthesized hybrid particles are biocompatible and might be useful for magnetic transport and hyperthermia studies.

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The calcium-sensing receptor (CaSR) plays an important role in sensing extracellular calcium ions and regulating parathyroid hormone secretion by parathyroid gland cells, and the receptor is a suitable target for the treatment of hyperparathyroidism. Cinacalcet hydrochloride is a representative CaSR agonist which widely used for the hyperparathyroidism. However, it has several issues to clinical use, such as nausea/vomiting and strong inhibition of CYP2D6. We tried to improve these issues of cinacalcet for a new pharmaceutical agent as a preferable CaSR agonist. Optimization from cinacalcet resulted in the identification of pyrrolidine compounds and successfully led to the discovery of evocalcet as an oral allosteric CaSR agonist. Evocalcet, which exhibited highly favorable profiles such as CaSR agonistic activity and good DMPK profiles, will provide a novel therapeutic option for secondary hyperparathyroidism.