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As one of the most extensively studied glycosaminoglycan lyases, heparinase I has been used in producing low or ultra-low molecular weight heparin. Its' important applications are to neutralize the heparin in human blood and analyze heparin structure in the clinic. However, the low productivity and activity of the enzyme have greatly hindered its applications. In this study, a novel Hep-I from Bacteroides cellulosilyticus (BcHep-I) was successfully cloned and heterologously expressed in E. coli BL21 (DE3) as a soluble protein. The molecular mass and isoelectric point (pI) of the enzyme are 44.42 kDa and 9.02, respectively. And the characterization of BcHep-I after purified with Ni-NTA affinity chromatography suggested that it is a mesophilic enzyme. BcHep-I can be activated by 1 mM Ca2+, Mg2+, and Mn2+, while severely inhibited by Zn2+, Co2+, and EDTA. The specific activity of the enzyme was 738.3 U⋅mg-1 which is the highest activity ever reported. The Km and Vmax were calculated as 0.17 mg⋅mL-1 and 740.58 U⋅mg-1, respectively. Besides, the half-life of 300 min at 30°C showed BcHep-I has practical applications. Homology modeling and substrate docking revealed that Gln15, Lys74, Arg76, Lys104, Arg149, Gln208, Tyr336, Tyr342, and Lys338 were mainly involved in the substrate binding of Hep-I, and 11 hydrogen bonds were formed between heparin and the enzyme. These results indicated that BcHep-I with high activity has great potential applications in the industrial production of heparin, especially in the clinic to neutralize heparin. [ABSTRACT FROM AUTHOR]

Background: There is much variation in hospice use with respect to geographic factors such as area-based deprivation, location of patient's residence and proximity to services location. However, little is known about how the association between geographic access to inpatient hospice and hospice deaths varies by patients' region of settlement. Study aim: To examine regional differences in the association between geographic access to inpatient hospice and hospice deaths. Methods: A regional population-based observational study in England, UK. Records of patients aged ≥ 25 years (n = 123088) who died from non-accidental causes in 2014, were extracted from the Office for National Statistics (ONS) death registry. Our cohort comprised of patients who died at home and in inpatient hospice. Decedents were allocated to each of the nine government office regions of England (London, East Midlands, West Midlands, East, Yorkshire and The Humber, South West, South East, North West and North East) through record linkage with their postcode of usual residence. We defined geographic access as a measure of drive times from patients' residential location to the nearest inpatient hospice. A modified Poisson regression estimated the association between geographic access to hospice, comparing hospice deaths (1) versus home deaths (0). We developed nine regional specific models and adjusted for regional differences in patient's clinical & socio-demographic characteristics. The strength of the association was estimated with adjusted Proportional Ratios (aPRs). Findings: The percentage of deaths varied across regions (home: 86.7% in the North East to 73.0% in the South East; hospice: 13.3% in the North East to 27.0% in the South East). We found wide differences in geographic access to inpatient hospices across regions. Median drive times to hospice varied from 4.6 minutes in London to 25.9 minutes in the North East. We found a dose-response association in the East: (aPRs: 0.22–0.78); East Midlands: (aPRs: 0.33–0.63); North East (aPRs: 0.19–0.87); North West (aPRs: 0.69–0.88); South West (aPRs: 0.56–0.89) and West Midlands (aPRs: 0.28–0.92) indicating that decedents who lived further away from hospices locations (≥ 10 minutes) were less likely to die in a hospice. Conclusion: The clear dose-response associations in six regions underscore the importance of regional specific initiatives to improve and optimise access to hospices. Commissioners and policymakers need to do more to ensure that home death is not due to limited geographic access to inpatient hospice care. [ABSTRACT FROM AUTHOR]