A Schistosoma japonicum chimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens

<p>Abstract</p> <p>Background</p> <p>Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4) via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice.</p> <p>Methods</p> <p>The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3⁺CD8^-IFN-γ⁺cells and CD3⁺CD8^-IL-4⁺cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge.</p> <p>Results</p> <p>Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced a significant reduction in liver egg deposition at 47.0–50.3% and the number of liver eggs per female at 34.5–37.2% but less effect on worm burdens at only 17.3–23.1%, whereas no effect of the formulations with other adjuvants on the number of liver eggs per female was observed.</p> <p>Conclusion</p> <p>Construction of polyvalent subunit vaccine was capable to enhance immunogenicity and protection efficacy against schistosomiasis. There was correlation of the polarized Th1 response with reduction of liver egg burdens, supporting the immune deviation strategy for schistosomiasis japonica vaccine development.</p

Enhancing Event Sequence Modeling with Contrastive Relational Inference

Neural temporal point processes(TPPs) have shown promise for modeling continuous-time event sequences. However, capturing the interactions between events is challenging yet critical for performing inference tasks like forecasting on event sequence data. Existing TPP models have focused on parameterizing the conditional distribution of future events but struggle to model event interactions. In this paper, we propose a novel approach that leverages Neural Relational Inference (NRI) to learn a relation graph that infers interactions while simultaneously learning the dynamics patterns from observational data. Our approach, the Contrastive Relational Inference-based Hawkes Process (CRIHP), reasons about event interactions under a variational inference framework. It utilizes intensity-based learning to search for prototype paths to contrast relationship constraints. Extensive experiments on three real-world datasets demonstrate the effectiveness of our model in capturing event interactions for event sequence modeling tasks.Comment: 6 pages, 2 figure

An “In-Depth” Description of the Small Non-coding RNA Population of Schistosoma japonicum Schistosomulum

Parasitic flatworms of the genus Schistosoma are the causative agents of schistosomiasis, which afflicts more than 200 million people yearly in tropical regions of South America, Asia and Africa. A promising approach to the control of this and many other diseases involves the application of our understanding of small non-coding RNA function to the design of safe and effective means of treatment. In a previous study, we identified five conserved miRNAs from the adult stage of Schistosoma japonicum. Here, we applied Illumina Solexa high-throughput sequencing methods (deep sequencing) to investigate the small RNAs expressed in S. japonicum schistosomulum (3 weeks post-infection). This has allowed us to examine over four million sequence reads including both frequently and infrequently represented members of the RNA population. Thus we have identified 20 conserved miRNA families that have orthologs in well-studied model organisms and 16 miRNA that appear to be specific to Schistosoma. We have also observed minor amounts of heterogeneity in both 3′ and 5′ terminal positions of some miRNA as well as RNA fragments resulting from the processing of miRNA precursor. An investigation of the genomic arrangement of the 36 identified miRNA revealed that seven were tightly linked in two clusters. We also identified members of the small RNA population whose structure indicates that they are part of an endogenously derived RNA silencing pathway, as evidenced by their extensive complementarities with retrotransposon and retrovirus-related Pol polyprotein from transposon

THE EDUCATION-HEALTH NEXUS: A META-ANALYSIS

This file contains do commands, smcl and study list of the Manuscript entitled "The Education-Health nexus: A meta-analysis". The data will be posted once the manuscript is accepted for publication

Social capital and health in China: exploring the mediating role of lifestyle

Abstract Background Although social capital as a key determinant of health has been well established in various studies, little is known about how lifestyle factors mediate this relationship. Understanding the cross-relationships between social capital, health, and lifestyle factors is important if health promotion policies are to be effective. The purpose of this study is to explore whether different dimensions of social capital and lifestyle factors are related, and whether lifestyle factors mediate the association between social capital and self-rated health (SRH) and psychological well-being (PWB) in China. Methods This study used nationally representative data from the 2014 China Family Panel Studies (n = 28,916). The data reported on three dimensions of individual-level social capital: social trust, social relationship and Chinese Communist Party (CCP) membership. Health was assessed using SRH and PWB. Five lifestyle indicators were recorded: healthy diet, physical activity, smoking, sleeping, and non-overweight status. Logistic regression was used to examine the associations between social capital and lifestyle factors, and whether there was a mediating role of lifestyle. Odds ratios relating health status to social capital were reported before and after adjustment for lifestyle factors. Mediation analysis was then used to calculate the total, direct and indirect effects of social capital on SRH and PWB. Results The results show that social trust was significantly associated with all five lifestyle factors. Social relationship was significantly associated with four of the five: healthy diet, physical activity, sleeping and non-overweight. CCP membership was only significantly associated with two lifestyle factors: physical activity and non-overweight. Social trust and social relationship were significantly related to both SRH and PWB. CCP membership was only significantly related to SRH. Mediation analysis found modest evidence that lifestyle factors influenced the relationship between all three types of social capital and SRH. In contrast, only social trust and social relationship, but not CCP membership, were mediated by lifestyle factors with respect to PWB. Conclusions This study is the first to explore the mediating role of lifestyle factors in the relationship between social capital and health in China. The overall findings suggest that lifestyle factors modestly mediate the association between social capital and health. The degree of mediating effect varies across different dimensions of social capital. Social capital-based health promotion policies would benefit from taking lifestyle factors into account

The Relationship Between Social Capital and Self-reported Health in China

This paper uses the 2005 and 2006 China General Social Survey (CGSS) to study the relationship between social capital and self-reported health in China. It is the most comprehensive analysis of this subject to date, both in the sizes of the samples it analyses, in the number of social capital variables it investigates, and in its treatment of endogeneity. The authors identify social trust, social relationships, and social networks as important determinants of self-reported health. The magnitude of the estimated effects are economically important, in some cases being of the same size or larger than the effects associated with age and income. Their findings suggest that there is scope for social capital to be a significant policy tool for improving health outcomes in China