Discovery of 2,5-diphenyl-1,3,4-thiadiazole derivatives as HDAC inhibitors with DNA binding affinity.

Incorporating a DNA-binding fragment in HDAC inhibitors has been proved to be an effective strategy for the treatment of hematologic malignancies by our group. However, similar to other approved HDAC inhibitors, their effects on solid tumor were poor. For this issue, a series of 2,5-diphenyl-1,3,4-thiadiazole hydroxamate derivatives were designed and synthesized as the HDAC inhibitors with DNA binding affinity. Among the target compounds, 4j not only bound with DNA effectively but also exhibited the most potent inhibitory activity against HDAC1 with the IC50 of 15 nM. Compared to SAHA, compound 4j displayed stronger antiproliferative activity in tested tumor cell lines. Western blot analysis showed that 4j could enhance the acetylation of histone H3 and α-tubulin, as well as promote the activation of caspase 3 in HCT116 and MC38 cell lines. Furthermore, these responses resulted in significant suppression of tumor growth in the MC38 tumor model. This work validated that compound 4j was a promising lead compound for further structural optimization.

Corrigendum to: Willingness to use community health centres for initial diagnosis: the role of policy incentives among Chinese patients.

The aim of the study is to investigate the effect of policy incentives on residents' willingness to use community health centres for initial diagnosis. A cross-sectional survey with specific multiple price-list experiments was conducted in Guizhou, China. We were able to use in-depth individual interviews with a total of 422 participants. Our results showed that both financial and non-financial policy incentives can facilitate the utilisation of the community health centres. Approximately 60% of the respondents reported an increase in their willingness to use community health centres after the presentation of the financial policy, whereas 50% of respondents expressed an increase in their willingness to use community health centres with the non-financial policy. However, to some specific subgroups, such as residents with low trust, residents without chronic disease, residents with less healthcare visits and risk-averters, the impact of policy incentives were limited. The policy incentives are useful tools to attract more visitors to community health centres for initial diagnosis; however, their incentive effects vary in different subgroups. Thus, to change patients' perceptions regarding healthcare provider choice for initial diagnosis, policymakers should consider the heterogeneous responses of patients to policy incentives and focus their efforts on key cohorts.

Willingness to use community health centres for initial diagnosis: the role of policy incentives among Chinese patients.

The aim of the study is to investigate the effect of policy incentives on residents' willingness to use community health centres for initial diagnosis. A cross-sectional survey with specific multiple price-list experiments was conducted in Guizhou, China. We were able to use in-depth individual interviews with a total of 422 participants. Our results showed that both financial and non-financial policy incentives can facilitate the utilisation of the community health centres. Approximately 60% of the respondents reported an increase in their willingness to use community health centres after the presentation of the financial policy, whereas 50% of respondents expressed an increase in their willingness to use community health centres with the non-financial policy. However, to some specific subgroups, such as residents with low trust, residents without chronic disease, residents with less healthcare visits and risk-averters, the impact of policy incentives were limited. The policy incentives are useful tools to attract more visitors to community health centres for initial diagnosis; however, their incentive effects vary in different subgroups. Thus, to change patients' perceptions regarding healthcare provider choice for initial diagnosis, policymakers should consider the heterogeneous responses of patients to policy incentives and focus their efforts on key cohorts.

A Novel Hybrid Algorithm for Multiobjective Location-Allocation Problem in Emergency Logistics.

Increased frequency of disasters keeps reminding us of the importance of effective resource distribution in postdisaster. To reduce the suffering of victims, this paper focuses on how to establish an effective emergency logistics system. We first propose a multiobjective optimization model in which the location and allocation decisions are made for a three-level logistics network. Three objectives, deprivation costs, unsatisfied demand costs, and logistics cost, are adopted in the proposed optimization model. Several cardinality and flow balance constraints are considered simultaneously. Then, we design a novel effective IFA-GA algorithm by combining the firefly algorithm and genetic algorithm to solve this complex model effectively. Furthermore, three schemes are proposed to improve the effectiveness of the IFA-GA algorithm. Finally, the numerical results provide several insights on the theory and practice of relief distribution, which also illustrate the validity of the proposed solution algorithm.

Characterization of alginase and elicitor-active oligosaccharides from Gracilibacillus A7 in alleviating salt stress for Brassica campestris L.

Alginase was purified from Gracilibacillus A7 and evaluated for its ability to produce elicitor-active oligosaccharides. The optimum conditions for the alginase reaction are as follows: temperature, 40 °C; pH, 8.0; alginate content, 0.3-0.7%; and the presence of Na(+) and Mg(2+) metal ions. The degree of polymerization (DP) decreased as the reaction time of the alginase progressed, achieving values of 5.4 and 3.3 after 240 and 300 min, respectively. The relative root length (RRL) of the Brassica campestris L. increased with the addition of oligosaccharides with reduced DP values. The oligosaccharides with lower DP values are effective in reducing the effect of salt stress on the activity of the superoxide dismutase (SOD) and guaiacol peroxidase (POD), and oligosaccharides with moderate DP values can reduce the increase in lipid peroxidation activities (as malondialdehyde content) induced by salt stress. These results suggest that oligosaccharides may act as osmoprotective agents during the plant germination process.