ferent test groups. Mutations in the gene encoding the glycogen phosphatase laforin result in the fatal childhood dementia Lafora disease (LD). A cellular hallmark of LD is cytoplasmic, hyper-phosphorylated, glycogen-like aggregates called Lafora bodies (LBs) that form in nearly all tissues and drive disease progression. mTOR inhibitor Additional tools are needed to define the cellular function of laforin, understand the pathological role of laforin in LD, and determine the role of glycogen phosphate in glycogen metabolism. In this work, we present the generation and characterization of laforin nanobodies, with one being a laforin inhibitor. We identify multiple classes of specific laforin-binding nanobodies and determine their binding epitopes using hydrogen deuterium exchange (HDX) mass spectrometry. Using para-nitrophenyl phosphate (pNPP) and a malachite gold-based assay specific for glucan phosphatase activity, we assess the inhibitory effect of one nanobody on laforin's catalytic activity. Six families of laforin nanobodies are characterized and their epitopes mapped. One nanobody is identified and characterized that serves as an inhibitor of laforin's phosphatase activity. The six generated and characterized laforin nanobodies, with one being a laforin inhibitor, are an important set of tools that open new avenues to define unresolved glycogen metabolism questions.The six generated and characterized laforin nanobodies, with one being a laforin inhibitor, are an important set of tools that open new avenues to define unresolved glycogen metabolism questions. It is unclear whether vitamin D status is related to cardiovascular risk beyond that explained by conventional risk markers. We examined the relationship between serum 25-hydroxy (OH) vitamin D and incident cardiovascular disease (CVD; heart attack/stroke) after adjusting for individual- and community-level covariates from laboratory, administrative and survey data. Patients receiving their first 25-OH vitamin D test in Calgary, Alberta from 2009 to 2013 without a past CVD diagnosis but an electrocardiogram and body mass index (BMI) +/- 3months from testing were included. The following was merged to this data first results for laboratory-measured CVD risk markers (lipid profile, fasting plasma glucose, and HbA1c) measured +/- 3months from testing; Census Dissemination Area (CDA)-level indicators of socioeconomic status (SES) in 2011; and CVD diagnoses>3months from testing between 2009 and 2016. Linear and Poisson regression were used to examine associations between 25-OH vitamin D quartile and covariates, and Cox proportional hazard models were used to examine associations with incident CVD before and after adjusting for covariates. Among 72 348 patients, there were 1898 CVD events over a median of 6.0years. Increasing quartile of 25-OH vitamin D was associated with improved lipid and glycemic profiles (p<0.01), higher proportion of CDA-level indicators of high SES (p<0.01), and a lower risk of CVD (Q4 vs Q1 HR 0.72, 95% CI 0.63-0.81, p for trend<0.01) after adjusting for age, sex and average daily hours of sunlight during month of testing. The association with CVD was unchanged after adjusting for BMI, slightly attenuated after adjusting for SES but completely abolished after adjusting for laboratory-measured cardiovascular risk markers. Vitamin D status likely offers no additional information on CVD risk over conventional laboratory-measured risk markers.Vitamin D status likely offers no additional information on CVD risk over conventional laboratory-measured risk markers.Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies. The aim of this study was to evaluate the value of PON-1 activity in the diagnosis and monitoring of neonatal sepsis. Serum PON-1 activity, as paraoxonase and arylesterase, was prospectively studied in 48 septic neonates and matched controls. PON-1 activity was decreased at the acute phase of sepsis in comparison with values at recovery and values in controls. Paraoxonase or arylesterase at enrollment correlated significantly with serum Amyloid-A, CRP and IL-6 and could also discriminate septic than non-septic neonates. In conclusion, our results are promising regarding the role of PON-1 as a biomarker of neonatal sepsis. Larger studies are needed to validate the clinical utility of PON-1 in neonatal medicine.Zingiberis Rhizome Carbonisata (ZRC) has been used as a hemostatic agent in traditional Chinese medicine (TCM). However, the underlying molecular mechanism remains unclear. In this study, network pharmacology method was used to predict the potential mechanism of ZRC on hemostasis, based on the structures of the main compounds. Then, iTRAQ-based quantitative proteomics analysis was used for verification of the candidate target proteins and pathways to illustrate the underlying mechanisms. Furthermore, the differentially expressed proteins (DEPs) in the enriched pathways were validated by Enzyme-linked immunosorbent assay. The results showed that the hemostasis mechanism of ZRC may be related to Platelet activation, Rap1 signaling pathway and Complement and coagulation cascades. And 10 proteins (Fermt3, ACTB, Talin, αIIbβ3, Fga, Fgb, Fgg, FXIIIb, Kng and PLC-β were identified as the target DEPs) are considered as the key factors related to hemostatic efficacy of ZRC. Thus, integrated network pharmacology and quantitative proteomics technology were applied for the effective illuminating the molecular mechanisms of Chinese material medica.Memantine is the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, used in the treatment of Alzheimer's disease. It is also known that memantine pretreatment assured protection of skeletal muscles from poisoning with nerve agents and an interaction between memantine and AChE was proposed. In the study presented we examined interactions of memantine and its main metabolite (1-amino-3-hydroxymethyl-5-methyl adamantine, Mrz 2/373) with AChE in vitro as well as their effect on kinetics of the soman-induced AChE inhibition and aging. The results have shown that memantine and Mrz 2/373 exerted concentration-dependent inhibition of AChE, with Mrz 2/373 being a more potent inhibitor than the parent compound. Addition of soman 7.5 nmol/l induced gradual AChE inhibition that became almost complete after 20 min. Memantine (0.1, 0.5 and 1 mmol/l) and Mrz 2/373 (0.1, 0.5 and 1 mmol/l) concentration-dependently slowed down the AChE inhibition. After 30 min of incubation of AChE with soman, 5 min of aging and 20 min of reactivation by asoxime (HI-6 dichloride), AChE activity was 8.