Changes in the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios before and after percutaneous coronary intervention and their impact on the prognosis of patients with acute coronary syndrome

OBJECTIVES: This study aimed to prospectively observe the changes in the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) before and after percutaneous coronary intervention (PCI) and their impact on the prognosis of patients with acute coronary syndrome (ACS). METHODS: Blood samples from 205 patients with ACS were collected at admission and at 24h and 30 days postPCI to observe changes in the complete blood count. The Cox multivariate regression model was used to analyze the factors influencing major adverse cardiac events (MACE) after PCI in patients with ACS. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of inflammation indicators for MACE after PCI. RESULTS: Following PCI, NLR and PLR first increased postoperatively and then decreased within 30 days after PCI. Cox multivariate regression analysis showed that NLR and PLR at 24h post-PCI and acute ST-segment elevation myocardial infarction were independent influencing factors for the incidence of MACE after PCI. The ROC curve analysis showed that the NLR at 24h post-PCI was a better predictor of the incidence of MACE. The NLR at 24h post-PCI was significantly correlated with the number and length of implanted stents and operation duration. CONCLUSIONS: After PCI, patients with ACS had an increased neutrophil proportion and NLR. The NLR at 24h post-PCI was a better predictor of the incidence of postoperative MACE

Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming

SummaryObtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2−/−/γc−/− mice and secrete more than 300 μg/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications

Long-term functional maintenance of primary human hepatocytes in vitro

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.</p

A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts

Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.</p

Statistical Parsimony Networks and Species Assemblages in Cephalotrichid Nemerteans (Nemertea)

BACKGROUND: It has been suggested that statistical parsimony network analysis could be used to get an indication of species represented in a set of nucleotide data, and the approach has been used to discuss species boundaries in some taxa. METHODOLOGY/PRINCIPAL FINDINGS: Based on 635 base pairs of the mitochondrial protein-coding gene cytochrome c oxidase I (COI), we analyzed 152 nemertean specimens using statistical parsimony network analysis with the connection probability set to 95%. The analysis revealed 15 distinct networks together with seven singletons. Statistical parsimony yielded three networks supporting the species status of Cephalothrix rufifrons, C. major and C. spiralis as they currently have been delineated by morphological characters and geographical location. Many other networks contained haplotypes from nearby geographical locations. Cladistic structure by maximum likelihood analysis overall supported the network analysis, but indicated a false positive result where subnetworks should have been connected into one network/species. This probably is caused by undersampling of the intraspecific haplotype diversity. CONCLUSIONS/SIGNIFICANCE: Statistical parsimony network analysis provides a rapid and useful tool for detecting possible undescribed/cryptic species among cephalotrichid nemerteans based on COI gene. It should be combined with phylogenetic analysis to get indications of false positive results, i.e., subnetworks that would have been connected with more extensive haplotype sampling

A new species of Thermanemertes from Kairei hydrothermal vent field, Central Indian Ridge

http://www.godac.jamstec.go.jp/darwin/cruise/yokosuka/yk16-e02/

Study of Working Medium Performance by Acoustic Emission in EDM Machining of Ti6Al4V

In electrical discharge machining (EDM), the working medium plays an important role in the material removal process. Lots of methods have been utilized to study this process, but a widely accepted explanation about this process has not been yet accomplished. In this study, the acoustic emission (AE) sensor was fixed on EDM machine to study the material removal process by observing the expansion and contraction process of gas bubble surrounding the discharge plasma. The machining performance in different working mediums was studied for Ti-6Al-4V machining in air, kerosene, and water-based emulsion. Discharge in different working mediums would result in different material removal rates and surface quality. The difference of AE wave frequency domain distribution for discharge in different working mediums was studied. It was observed that the frequency of acoustic emission wave generated by discharge in different working mediums would be different. The characteristic difference of single AE wave generated by discharge in air, kerosene, and water-based emulsion was compared. It was found that the duration time and peak amplitude of acoustic emission wave generated by discharge in different working mediums were different, and the acoustic emission wave generated by discharge in water-based emulsion would last longer and get higher peak amplitude compared to discharge in air and kerosene. The significant difference of AE wave generated by discharge in water-based emulsion from that in kerosene was found. Based on the acoustic emission wave observation, the special characteristic of the material removal process for discharge in water-based emulsion was found