Drug delivery system based on metal-organic framework improved 5-Fluorouracil against spring viremia of carp virus.

Spring viremia of carp virus (SVCV), as a high pathogenicity pathogen, has seriously restricts the healthy and sustainable development of cyprinid farming industry. In this study, we selected 5-Fluorouracil (5-Fu) as the drug model based on zeolitic imidazolate framework-8 (ZIF-8) to construct a drug delivery system (5-Fu@ZIF-8), and the anti-SVCV activity was detected in vitro and in vivo. The results showed 5-Fu@ZIF-8 was uniform cubic particle with truncated angle and smooth surface, and the particle size was 90 nm. The anti-SVCV activity in vitro results showed that the highest inhibition rate of 5-Fu was 77.93% at 40 mg/L and the inhibitory concentration at half-maximal activity (IC50) was 20.86 mg/L. For 5-Fu@ZIF-8, the highest inhibition rate was 91.36% at 16 mg/L, and the IC50 value was 5.85 mg/L. In addition, the cell viability was increased by 18.1% after 5-Fu treatment. Similarly, after 5-Fu@ZIF-8 treatment, the cell viability increased by 27.3%. Correspondingly, in vivo experimental results showed the viral loads reduced by 18.1% on the days 7 and the survival rate increased to 19.4% at 80 mg/L after 5-Fu treatment. For 5-Fu@ZIF-8, the viral loads reduced by 41.2% and the survival rate increased to 54.8%. Mechanistically, 5-Fu inhibits viral replication by regulating p53 expression and promoting early apoptosis in infected cells. All results indicated that 5-Fu@ZIF-8 improved the anti-SVCV activity; it may be a potential strategy to construct a drug-loaded system with ZIF-8 as a carrier for the prevention and treatment of aquatic diseases.

Interaction of tinnitus suppression and hearing ability after cochlear implantation.

OBJECTIVES: To study the postoperative impact of cochlear implants (CIs) on tinnitus, as well as the impact of tinnitus on speech recognition with CI switched on. METHODS: Fifty-two postlingual deafened CI recipients (21 males and 31 females) were assessed using an established Tinnitus Characteristics Questionnaire and Tinnitus Handicap Inventory (THI) before and after cochlear implantation. The tinnitus loudness was investigated when CI was switched on and off in CI recipients with persistent tinnitus. The relation between tinnitus loudness and recipients' satisfaction of cochlear implantation was analyzed by the visual analogue scale (VAS) score. RESULTS: With CI 'OFF', 42 CI recipients experienced tinnitus postimplant ipsilaterally and 44 contralaterally. Tinnitus was totally suppressed ipsilateral to the CI with CI 'ON' in 42.9%, partially suppressed in 42.9%, unchanged in 11.9% and aggravated in 2.4%. Tinnitus was totally suppressed contralaterally with CI 'ON' in 31.8% of CI recipients, partially suppressed in 47.7%, unchanged in 20.5%. Pearson correlation analysis showed that tinnitus loudness and the results of cochlear implant patients satisfaction was negatively correlated (r = .674, p < .001). CONCLUSION: The study suggests six-month CI activation can be effective for suppressing tinnitus. The tinnitus loudness may affect patients' satisfaction with the use of CI.