We report a rational design and mechanism studies of mitochondria-immobilized iridium(iii) complexes that can kill cancer cells by targeting mitochondrial metabolism.

To reveal the impact of different feeding modes on the flavor quality of female Chinese mitten crab (Eriocheir sinensis) this study was conducted to compare the sensory evaluation scores, flavor compounds in meat and hepatopancreas of female E. sinensis fed with 3 feeding modes, that is, natural diets (NDs), traditional diets (TDs), and formulated diets (FDs). The result showed that crabs fed with ND had significantly lower sensory scores than the other 2 feeding modes in both edible tissues. The odor and taste profiles were evaluated by Electronic nose (E-nose) and tongue (E-tongue) techniques, respectively; results of perchloric acid showed each edible tissue had significant differences among the 3 modes. Contents of volatile compounds were measured by Headspace-solid phase micro extraction combined with gas chromatography-mass spectrometer. A total of 35 and 44 volatile compounds were identified in meat and hepatopancreas, respectively. ND mode of meat had the highest relative odor activity value (ROAV) summation among the 3 diet modes. TD mode of hepatopancreas had significantly higher ROAV summations. Based on the analysis of free amino acids and 5'-nucleotides, nonvolatile compounds were evaluated by equivalent umami concentration (EUC) and taste active values (TAVs) methods. For both meat and hepatopancreas, TD had the highest contents of umami amino acid, as for the 5'-nucleotide, FD had the highest 5'-inosin monophosphate concentrations. Overall, the EUC and TAVs of TD were higher than that of FD, whereas ND mode had the lowest values in the 2 edible tissues. In conclusion, TD mode had the best performance in terms of sensory evaluation, ROAVs of aroma-active compounds, and nonvolatile active compounds.

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Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir­(III) complexes Ir1–Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1–Ir6 show much higher cytotoxicity than cisplatin and they can effectively localize to mitochondria. Among them, complexes Ir3 and Ir4 with dipyrido­[3,2-a:2′,3′-c]­phenazine (dppz) ligands can bind to DNA tightly in vitro, intercalate to mtDNA in situ, and induce mtDNA damage. Ir3- and Ir4-impaired mitochondria exhibit decline of mitochondrial membrane potential, disability of adenosine triphosphate generation, disruption of mitochondrial energetic and metabolic status, which subsequently cause protective mitophagy, G0/G1 phase cell cycle arrest, and apoptosis. In vivo antitumor evaluations also show that Ir4 can inhibit tumor xenograft growth effectively. Overall, our work proves that targeting the mitochondrial genome may present an effective strategy to develop metal-based anticancer agents to overcome cisplatin resistance.

ObjectiveTo compare corneal biomechanical properties, measured by a newly developed tonometer (Corneal Visualization Scheimpflug Technology, Corvis ST), in untreated primary open angle glaucoma (POAG) patients, POAG patients with long-term topical prostaglandin analog (PGA) therapy and in normal controls. Further is to investigate the potential effects of PGA on corneal biomechanics.MethodsIn this case-control study, 35 consecutive medication naïve eyes with POAG, 34 POAG eyes with at least 2 years treatment by PGA and 19 normal eyes were included. Intraocular pressure (IOP), central corneal thickness (CCT) and corneal biomechanical parameters, including deformation amplitude (DA), applanation time (AT1 and AT2), applanation length (AL1 and AL2), applanation velocity (AV1 and AV2), and peak distance and radius were measured using Corvis ST. Axial length and corneal curvature were measured with partial coherence interferometry (IOLMaster, Zeiss, Germany). General linear model analysis was performed to investigate the corneal biomechanical property changes among the normal controls, newly diagnosed POAG patients and POAG patients with long-term PGA treatment, and among the subgroups of different types of PGA treatment, including bimatoprost, latanoprost and travoprost. Furthermore, pairwise comparisons using Bonferroni correction for least squares means were employed.ResultsAT1 (p<0.0001), AV1 (p<0.0001), AT2 (p = 0.0001), AV2 (p<0.0001) and DA (p = 0.0004) in newly diagnosed glaucoma patients were significantly different from those in normal subjects and in patients underwent at least 2 years topical PGA therapy after adjusting for age and gender. After adjusting for age, gender, IOP, CCT, axial length and corneal curvature, a significant difference was detected for DA between glaucoma patients without PGA treatment and patients with long-term PGA therapy (p = 0.0387). Furthermore, there were no statistical significant differences in all of the corneal biomechanical parameters among the 3 types of PGA therapy subgroups, namely bimatoprost, latanoprost and travoprost.ConclusionsSignificant changes in corneal deformation parameters were found among untreated POAG patients, POAG patients with long-term topical PGA therapy and normal controls. Long-term topical PGA treatment might have a direct effect on corneal biomechanical properties in addition to the indirect effect owing to the PGA-induced IOP reduction and CCT decrease on corneal dynamic properties.