Research on the Standardization of Drug Test Data

In order to solve the problems that test data of the drug control institution is not standardized and low quality, the data exchange and information sharing are realized, the data value is mined and the information level is improved. Method: combined with the business of control institution and information practice, refer to the practice of relevant standard development; carry out the research on standard development work from the content, principle and process. Result and conclusion: this research completes development of the local standard of Guangdong drug test data, which can provide reference for the development of similar standards in future

RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer

Ferroptosis is an iron-dependent, oxidative cell death, and is characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. It has been implicated in various human diseases, including cancer. Recently, ferroptosis, as a non-apoptotic form of cell death, is emerging in specific cancer types; however, its relevance in colorectal cancer (CRC) is unexplored and remains unclear. Here, we showed that ferroptosis inducer RSL3 initiated cell death and ROS accumulation in HCT116, LoVo, and HT29 CRC cells over a 24 h time course. Furthermore, we found that ROS levels and transferrin expression were elevated in CRC cells treated with RSL3 accompanied by a decrease in the expression of glutathione peroxidase 4 (GPX4), indicating an iron-dependent cell death, ferroptosis. Overexpression GPX4 resulted in decreased cell death after RSL3 treatment. Therefore, RSL3 was able to induce ferroptosis on three different CRC cell lines in vitro in a dose- and time-dependent manner, which was due to increased ROS and an increase in the cellular labile iron pool. Moreover, this effect was able to be reversed by overexpression of GPX4. Taken together, our results suggest that the induction of ferroptosis contributed to RSL3-induced cell death in CRC cells and ferroptosis may be a pervasive and dynamic form of cell death for cancer treatment

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Steady-state and emergency dendritic cell development at a clonal level

© 2019 Shuiping LinRecent clonal fate and single cell RNA-sequencing studies demonstrate that significant lineage imprinting is already in place within individual haematopoietic stem and progenitor cells (HSPCs). Dendritic cells (DCs) represent one such branch of haematopoiesis and are responsible for pathogen-sensing and activation of the adaptive immune response. At the population level, all three major DC subtypes including type 1 conventional DCs (cDC1s), type 2 conventional DCs (cDC2s) and plasmacytoid DCs (pDCs), can be generated from a restricted common DC progenitor (CDP) population downstream of HSPCs. However, recent clonal evidence has suggested earlier subtype-specific imprinting within the CDP and even early HSPC populations. Therefore, the current hierarchical model of haematopoiesis is insufficient to explain the complexity and dynamics of DC development. The aim of this thesis was to investigate the development of DCs at the single cell level. One caveat of most prior single cell lineage tracing studies was that clonal fate was only measured at a single time point. Therefore, questions remain as to whether the fate bias observed at a snapshot in time is consistent with earlier or later times. Here, using cellular barcoding, I develop an experimental and computational framework to allow robust periodical examination of lineage outputs of thousands of transient clones during DC development in vitro. I reveal that single HSPC clones are largely programmed regarding the types of DCs to make (fate), the number of DCs to produce (size), and when DC generation occurs (timing). Together, I define these unique properties as a clone’s cellular trajectory. Importantly, I demonstrate that a large proportion of early HSPCs are already committed towards either cDC or pDC generation, even when clonal output is measured over time. This finding is consistent with and further complements the most recent evidence of DC subtype imprinting during early haematopoiesis. Exogenous administration of Flt3 ligand (FL) is known to preferentially induce ‘emergency’ DC development, and is shown to provide promising therapeutic benefits in various conditions such as infection and cancer. However, how FL signals regulate cell proliferation and differentiation during early DC development is largely unknown. In this thesis, I investigate the clonal aetiology of this process. Using cellular barcoding, I demonstrate that emergency DC generation is predominantly driven by increased expansion of pre-existing HSPC clones that are already primed with DC potential. Consistently, enhanced cell cycle activity is found to be prominent within most early HSPCs after short exposure to FL. In particular, using a single cell multi-omics profiling approach, I identify key cellular and molecular events within a unique group of early HSPCs that are most responsive to FL stimulation, which include increased cell division, maintenance of hyper-proliferative potential and establishment of a DC lineage program. Collectively, the findings presented in this thesis provide new insights into the control and regulation of DC fate within individual HSPCs during steady-state and emergency haematopoiesis, with important implications regarding the maintenance or manipulation of DC generation in health and disease

The Influences of Consumer-to-Consumer Interaction on Dissatisfactory Consumers’ Repetitive Purchases in Network Communities

Consumer-to-consumer interaction is an important activity in network communities. Consumer-to-consumer interaction involves information interaction and social interaction, which greatly influences consumers’ experience and behaviors. The model of stimulus-organism-response (S-O-R) is usually applied to explain how environmental stimulus affects consumer behavior through the internal state. Thus, this research takes dissatisfactory consumers as the object, sets information interaction and social interaction as a stimulus, consumer knowledge and trust as an organism, and repetitive purchases as a response. It constructs a theoretical model that consumer-to-consumer interaction influences repetitive purchases through consumer knowledge and trust. In this study, the model and hypotheses were tested by analyzing 328 valid questionnaires. The results show that information interaction had a significant positive effect on consumer knowledge, while social interaction had no significant effect on consumer knowledge. Information interaction and social interaction each had significant positive effects on consumer trust. Consumer knowledge and trust each had significant positive effects on repetitive purchases. Consumer knowledge and trust played a partial mediating role between information interaction and repetitive purchase, respectively. Consumer knowledge had no mediating role between social interaction and repetitive purchases, while consumer trust played a complete mediating role between social interaction and repetitive purchases. The results revealed that the deep mechanism of consumer-to-consumer interaction’s influence on dissatisfactory consumers’ repetitive purchases in network communities further enriched consumers’ purchase behaviors, at least theoretically. This research also provided insights for network community marketing

The Influences of Consumer-to-Consumer Interaction on Dissatisfactory Consumers’ Repetitive Purchases in Network Communities

Consumer-to-consumer interaction is an important activity in network communities. Consumer-to-consumer interaction involves information interaction and social interaction, which greatly influences consumers’ experience and behaviors. The model of stimulus-organism-response (S-O-R) is usually applied to explain how environmental stimulus affects consumer behavior through the internal state. Thus, this research takes dissatisfactory consumers as the object, sets information interaction and social interaction as a stimulus, consumer knowledge and trust as an organism, and repetitive purchases as a response. It constructs a theoretical model that consumer-to-consumer interaction influences repetitive purchases through consumer knowledge and trust. In this study, the model and hypotheses were tested by analyzing 328 valid questionnaires. The results show that information interaction had a significant positive effect on consumer knowledge, while social interaction had no significant effect on consumer knowledge. Information interaction and social interaction each had significant positive effects on consumer trust. Consumer knowledge and trust each had significant positive effects on repetitive purchases. Consumer knowledge and trust played a partial mediating role between information interaction and repetitive purchase, respectively. Consumer knowledge had no mediating role between social interaction and repetitive purchases, while consumer trust played a complete mediating role between social interaction and repetitive purchases. The results revealed that the deep mechanism of consumer-to-consumer interaction’s influence on dissatisfactory consumers’ repetitive purchases in network communities further enriched consumers’ purchase behaviors, at least theoretically. This research also provided insights for network community marketing

Influences of Reference Group on Users’ Purchase Intentions in Network Communities: From the Perspective of Trial Purchase and Upgrade Purchase

Reference group is an important factor influencing users’ purchase in the network communities. The reference group’s influences involve informative influence and normative influence, and users’ purchases are divided into the trial purchase and upgrade purchase. In different purchases, users have different product information, consumer experience, and purchase attitudes, making different responses to the reference group. Thus, a research model of reference groups’ influences on users’ purchase intentions from the perspective of trial purchase and upgrade purchase is constructed. The model and hypotheses are tested by analyzing 349 valid questionnaires. The results indicate that both informative and normative influences have significant positive effects on users’ trial purchase intentions. Informative influence has a significant positive effect on users’ upgrade intentions, while the normative influence on users’ upgrade purchase intentions is not significant. Both informative influence and normative influence have significant positive effects on trust in the product. Trust in the product has a significant positive effect on trial purchase intentions, but its effect on upgrade purchase intentions is not significant. Purchase involvement positively regulates the relationship between informative influence and trial purchase intentions and negatively regulates the relationship between informative influence and upgrade purchase intentions. The results further enrich the theoretical system of users’ purchase behaviors in a virtual environment. The research can also have important implications for network communities wishing to improve online marketing

Impact Resistance Enhancement by Adding Core-Shell Particle to Epoxy Resin Modified with Hyperbranched Polymer

A core-shell particle was fabricated by grafting amino-terminated hyperbranched polymer to the surface of silica nanoparticles. The influences of core-shell particle contents on the tensile and impact strength of the epoxy thermosets modified with amino-terminated hyperbranched polymer were discussed in detail. For comparison, core-shell particle was added into the epoxy/polyamide system for toughness improvement. Results from tensile and impact tests are provided. The introduction of core-shell particle into the epoxy/polyamide systems just slightly enhanced the tensile and impact strength. The incorporation of 3 wt % core-shell particle could substantially improve the tensile and impact strength of epoxy/amino-terminated hyperbranched polymer thermosets. Field emission-scanning electron microscope images of the impact fracture surfaces showed that the excellent impact resistance of epoxy/amino-terminated hyperbranched polymer/core-shell particle thermosets may be attributed to the synergistic effect of shearing deformation and crack pinning/propagation, which is induced by the good compatibility between epoxy matrix and core-shell particle in the presence of amino-terminated hyperbranched polymer

Impact Resistance Enhancement by Adding Core-Shell Particle to Epoxy Resin Modified with Hyperbranched Polymer

A core-shell particle was fabricated by grafting amino-terminated hyperbranched polymer to the surface of silica nanoparticles. The influences of core-shell particle contents on the tensile and impact strength of the epoxy thermosets modified with amino-terminated hyperbranched polymer were discussed in detail. For comparison, core-shell particle was added into the epoxy/polyamide system for toughness improvement. Results from tensile and impact tests are provided. The introduction of core-shell particle into the epoxy/polyamide systems just slightly enhanced the tensile and impact strength. The incorporation of 3 wt % core-shell particle could substantially improve the tensile and impact strength of epoxy/amino-terminated hyperbranched polymer thermosets. Field emission-scanning electron microscope images of the impact fracture surfaces showed that the excellent impact resistance of epoxy/amino-terminated hyperbranched polymer/core-shell particle thermosets may be attributed to the synergistic effect of shearing deformation and crack pinning/propagation, which is induced by the good compatibility between epoxy matrix and core-shell particle in the presence of amino-terminated hyperbranched polymer