uced the increased expression level of senescence, and atherothrombotic markers at arterial sites at risk in the control lean, but not obese, ZSF1 rat.The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of L-lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from Clostridium acetobutylicum. L-lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTSGlc and PTSFru) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and L-lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered C. glutamicum strain K-8 capable of producing 221.3 ± 17.6 g/L L-lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of L-lysine production from mixed sugar. This is also the first report for improving the efficiency of L-lysine production by systematic modification of carbohydrate metabolism systems.BACKGROUND Gold standard microscopic examination of Plasmodium falciparum intraerythrocytic stage remains an important process for staging and enumerating parasitized erythrocytes in culture; however, microscopy is laborious and its accuracy is dependent upon the skill of the examiner. METHODS In this study, ViSafe Green (VSG), which is a nucleic acid-binding fluorescent dye, was used for assessing in vitro development of P. falciparum using flow cytometry. RESULTS Fluorescence intensity of VSG was found to depend on the developmental stage of parasites. Specifically, multiple-nuclei-containing schizonts were observed in the VSGhigh population, and growing trophozoites and ring-shaped forms were observed in the VSGintermediate and VSGlow populations. The efficacy of VSG-based assay was found to be comparable to the microscopic examination method, and it demonstrated an ability to detect as low as 0.001% of the parasitaemia estimated by Giemsa staining. Moreover, when applying VSG for anti-malarial drug test, it was able to observe the growth inhibitory effect of dihydroartemisinin, the front-line drug for malaria therapy. CONCLUSIONS Taken together, the results of this study suggest the VSG-based flow cytometric assay to be a simple and reliable assay for assessing P. falciparum malaria development in vitro.BACKGROUND To reduce hospitalization costs, it is necessary to prevent avoidable hospitalization as well as avoidable readmission. This study aimed to examine the relationship between clinic physician workforce and unplanned readmission for ambulatory care sensitive conditions (ACSCs). METHODS The present study was a retrospective database research using nationwide administrative claims database of acute care hospitals in Japan. We identified patients aged ≥65 years who were admitted with ACSCs from home and discharged to home between April 2014 and December 2014 (n = 127,209). The primary outcome was unplanned readmission for ACSCs within 30 or 90 days of hospital discharge. A hierarchical logistic regression model was developed with patients at the first level and regions (secondary medical service areas) at the second level. https://www.selleckchem.com/products/jtc-801.html RESULTS The 30-day and 90-day ACSC-related readmission rates were 3.7 and 4.6%, respectively. The high full-time equivalents (FTEs) of clinic physicians per 100,000 population were significantly associated with decreased odds ratios for 30-day and 90-day ACSC-related readmissions. This association did not change even when sensitivity analyses was conducted. CONCLUSIONS Among patients who had history of admission for ACSCs, greater clinic physician workforce prevented the incidence of readmission because of ACSCs. Regional medical plans to prevent avoidable readmissions should incorporate policy interventions that focus on the clinic physician workforce.BACKGROUND The polymer-based drug/gene delivery is promising for the treatment of inherent or acquire disease, because of the polymer's structural flexibility, larger capacity for therapeutic agent, low host immunogenicity and less cost. Antisense therapy is an approach to fighting genetic disorders or infections using antisense oligonucleotides (AOs). Unfortunately, the naked AOs showed low therapeutic efficacy in vivo and in clinical trial due to their poor cellular uptake and fast clearance in bloodstream. In this study, a series of triazine-cored amphiphilic polymers (TAPs) were investigated for their potential to enhance delivery of AOs, 2'-O-methyl phosphorothioate RNA (2'-OMePS) and phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. RESULTS TAPs significantly enhanced AO-induced exon-skipping in a GFP reporter-based myoblast and myotube culture system, and observed cytotoxicity of the TAPs were lower than Endoporter, Lipofectamine-2000 or PEI 25K. Application of optimized formulations of TAPs with AO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. The best ones for PMO and 2'-OMePS delivery have reached to 11-, 15-fold compared with the AO only in mdx mice, respectively. CONCLUSION The study of triazine-cored amphiphilic polymers for AO delivery in vitro and in mdx mice indicated that the carrier's performances are related to the molecular size, compositions and hydrophilic-lipophilic balance (HLB) of the polymers, as well as the AO's structure. Improved exon-skipping efficiency of AOs observed in vitro and in mdx mice accompanied with low cytotoxicity demonstrated TAP polymers are potentials as safe and effective delivery carrier for gene/drug delivery.