Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging.

Multivalent glycosidase inhibitors based on 1-deoxynojirimycin derivatives against α-glucosidases have been rapidly developed. Nonetheless, the mechanism based on self-assembled multivalent glucosidase inhibitors in living systems needs to be further studied. It remains to be determined whether the self-assembly possesses sufficient stability to endure transit through the small intestine and subsequently bind to the glycosidases located therein. In this paper, two amphiphilic compounds, 1-deoxynojirimycin and α-peptoid conjugates (LP-4DNJ-3C and LP-4DNJ-6C), were designed. Their self-assembling behaviors, multivalent α-glucosidase inhibition effect, and fluorescence imaging on living organs were studied. LP-4DNJ-6C exhibited better multivalent α-glucosidase inhibition activities in vitro. Moreover, the self-assembly of LP-4DNJ-6C could effectively form a complex with Nile red. The complex showed fluorescence quenching effect upon binding with α-glucosidases and exhibited potent fluorescence imaging in the small intestine. This result suggests that a multivalent hypoglycemic effect achieved through self-assembly in the intestine is a viable approach, enabling the rational design of multivalent hypoglycemic drugs.

Fluorescence sensing and glycosidase inhibition effect of multivalent glycosidase inhibitors based on Naphthalimide-deoxynojirimycin conjugates.

Synthetic glycoconjugates as chemical probes have been widely developed for the detection of glycosidase enzymes. However, the binding interactions between iminosugar derivatives and glycosidases were limited, especially for the binding interactions between multivalent glycosidase inhibitors and α-glycosidases. In this paper, three naphthalimide-DNJ conjugates were synthesized. Furthermore, the binding interactions and glycosidase inhibition effects of them were investigated. It was found that the strong binding interactions of multivalent glycosidase inhibitors with enzymes were related to the efficient inhibitory activity against glycosidase. Moreover, the lengths of the chain between DNJ moieties and the triazole ring for the naphthalimide-DNJ conjugates influenced the self-assembly properties, binding interactions and glycosidase inhibition activities with multisource glycosidases. Compound 13 with six carbons between the DNJ moiety and triazole ring showed the stronger binding interactions and better glycosidase inhibition activities against α-mannosidase (jack bean) and α-glucosidase (aspergillus niger). In addition, compound 13 showed an effective PBG inhibition effect in mice with 51.18 % decrease in blood glucose at 30 min. This result opens a way for detection of multivalent glycosidase inhibition effect by a fluorescent sensing method.

Multivalent glucosidase inhibitors based on perylene bisimide and iminosugar conjugates.

Although multivalent glucosidase inhibitors based on iminosugars have shown enhanced inhibition activity, an effective way to improve their hypoglycemic effect in vivo, is still in infancy and needs further development. In this paper, PBI-5DNJ and PBI-6DNJ, with three or four DNJ moieties respectively conjugated at the bay position were synthesized. PBI-6DNJ evidenced stronger π-π stacking interactions and, when self-assembled, a smaller size than that of PBI-5DNJ. It was found that PBI-6DNJ exhibited superior α-glucosidases (from mice) inhibition activity (Ki = 0.14 ± 0.007 µM) in vitro than that (Ki = 0.31 ± 0.01) of PBI-5DNJ and in vivo hypoglycemic effects in mice models. PBI-6DNJ possessed good hypoglycemic effects with the percentages of PBG levels of 40.40 ± 3.33% and 39.23 ± 4.84% at a dose of 2.0 mg/kg after 15 min and 30 min of administration, respectively. In terms of measuring percentage decrease of PBG level per DNJ unit, PBI-6DNJ displayed a 2.1-fold enhancement than miglitol, demonstrating a consistency between in vitro and in vivo experiments. This paves the way to the connection between in vivo hypoglycemic potency and in vitro glucosidase inhibition assay, leading to reliable and simplified assessment of hypoglycemic potency determination, and opening a basic understanding of the design of multivalent glucosidase inhibitors.

Evaluation index system of education quality for nursing professional degree postgraduate using the analytic hierarchy process.

ABSTRACT: Nursing is an inseparable job with the healthy life of human beings. High-level nursing talents have a greater influence on patients. It is the future trend for schools to train Nursing Professional Degree Postgraduate, and the evaluation of their education quality is the top priority.To construct the education quality evaluation index system of Nursing Professional Degree Postgraduate and to determine the weight of each indicator.Firstly, the indicators of the evaluation index system of education quality were identified from the literature review. Meanwhile, the Delphi questionnaire was designed and 13 experts evaluated and rated the indictors who were invited to conduct two rounds of the questionnaire. The weights associated with the factors were determined using the analytic hierarchy process and percentage methods, Finally, we developed the evaluation index system of education quality for a postgraduate nursing professional degree.The evaluation system consisted of 4 first-level indicators, 17 second-level indicators, and 71 third-level indicators. According to the weights computed by analytic hierarchy process, first-level indicators are ranked as "Input quality" (0.1273), "Process quality" (0.3111), "Output quality" (0.0846), "Development quality" (0.4770). Among the secondary indicators, experts pay the most attention to career development (0.3180). The top three indicators of third-level indicators are workplace (0.2385), matching degree between personal expectations and job opportunities (0.1272), and promotion opportunities (0.0795).The quality index system of nursing postgraduate education is scientific and reliable, and the weight distribution is reasonable. It is an effective tool for evaluating the quality of nursing graduate education.

Mediating effects of nurses 'personal and organizational values between organizational commitment and turnover: Cross-sectional study.

BACKGROUND: The values of individuals and organizations are the core factors driving and guiding nurses' decision-making and actions. Previous studies mainly focused on the impact of organizational commitment and other influencing factors on turnover intention. AIM: To explore the mediating effect of personal and organizational values matching the relationship between organizational commitment and turnover intention of nursing staff. METHODS: A cross-sectional survey of 490 subjects in four tertiary hospitals in Tianjin was conducted by convenient sampling. Multivariate regression analysis and structural equation models were used to test each hypothesis. RESULTS: The results showed that there is a negative correlation between personal and organizational values, organizational commitment and turnover intention, and personal and organizational values played an indirect intermediary role between organizational commitment and turnover intention. CONCLUSIONS: Organizational commitment reduces nurses' turnover intention indirect through personal and organizational values paths. Leaders can improve nurses' values as members of the organization, so as to participate in their own work more actively. IMPLICATIONS FOR NURSING MANAGEMENT: Managers should effectively reduce the turnover rate and stabilize the nursing team by improving the organizational commitment and personal and organizational values of clinical nurses.