Upregulated Expression of Cytotoxicity-Related Genes in IFN-γ Knockout Mice with Schistosoma japonicum Infection

It is well accepted that IFN-γ is important to the development of acquired resistance against murine schistosomiasis. However, the in vivo role of this immunoregulatory cytokine in helminth infection needs to be further investigated. In this study, parasite burden and host immune response were observed in IFN-γ knockout mice (IFNg KO) infected with Schistosoma japonicum for 6 weeks. The results suggested that deficiency in IFN-γ led to decreased egg burden in mice, with low schistosome-specific IgG antibody response and enhanced activation of T cells during acute infection. Microarray and qRT-PCR data analyses showed significant upregulation of some cytotoxicity-related genes, including those from the granzyme family, tumor necrosis factor, Fas Ligand, and chemokines, in the spleen cells of IFNg KO mice. Furthermore, CD8+ cells instead of NK cells of IFNg KO mice exhibited increased transcription of cytotoxic genes compared with WT mice. Additionally, Schistosoma japonicum-specific egg antigen immunization also could activate CD8+ T cells to upregulate the expression of cytotoxic genes in IFNg KO mice. Our data suggest that IFN-γ is not always a positive regulator of immune responses. In certain situations, the disruption of IFN-γ signaling may up-regulate the cytotoxic T-cell-mediated immune responses to the parasite

Multiple vaccinations with UV- attenuated cercariae in pig enhance protective immunity against Schistosoma japonicum infection as compared to single vaccination

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis japonica is a major public health problem in the endemic areas of China, the Philippines, and Indonesia. To date, a vaccine has not been developed against this disease but immunization with UV-attenuated cercariae can induce a high level of protective immunity in Landrace/Yorkshire/Duroc crossbred pigs. To compare the efficacy of a single vaccination and multiple vaccinations with UV-attenuated <it>Schistosoma japonicum </it>cercariae, two groups of pigs received either one or three exposures to 10,000 cercariae attenuated with 400 μw UV.</p> <p>Results</p> <p>Pigs with a single immunization had a 59.33% reduction in adult worm burden, a 89.87% reduction in hepatic eggs and a 86.27% reduction in fecal eggs at eight weeks post-challenge (<it>P </it>< 0.01). After three immunizations, protection increased to 77.62%, 88.8% and 99.78% reduction in adult worms, hepatic eggs and fecal eggs, respectively (<it>P </it>< 0.01). Humoral and cellular immunological parameters measured indicated that schistosome-specific IgG1 and IgG2 levels in the vaccinated groups were higher than in the infection-control group. Triple vaccinations resulted in higher levels of antibodies, especially IgG2, compared with a single vaccination and IFN-γ levels increased with repeated immunization with UV-irradiated cercariae.</p> <p>Conclusion</p> <p>The high levels of protection against <it>S. japonicum </it>infection can be achieved with a UV-attenuated vaccine in pigs, and that three vaccinations were possibly more effective than a single vaccination. Moreover, triple vaccinations evoked a more vigorous IFN-γ response and a stronger antibody-mediated response, especially an increase in the levels of IgG2 antibodies.</p

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study.

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5?years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1?×?gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective

Immune Events Associated with High Level Protection against Schistosoma japonicum Infection in Pigs Immunized with UV-Attenuated Cercariae

BACKGROUND: The vaccination of radiation-attenuated Schistosoma japonicum cercariae can induce effective protection in artiodactyl, but the immune events related to protective immunity are not fully understood. To provide a paradigm for a human recombinant antigen vaccine, we have undertaken a vaccination and challenge experiment in pigs, which was recognized as an appropriate animal model in this type of study because of their similarity to human in immunology, and investigated the relative immune events induced by the radiation-attenuated S. japonicum cercariae. METHODS AND FINDINGS: We found that pigs immunized once with 400 µw UV-irradiated cercariae exhibited 63.84% and 71.82% reductions in worm burden and hepatic eggs respectively. Protective immunity in vaccinated pigs was associated with high level productions of IgM, total IgG, IgG1 and IgG2; IgG2 was significantly increased in the acute infection. IFN-γ levels could be elicited by immunization. At week 6 post-infection, IFN-γ, IL-4 and IL-10 levels also showed a dramatic rise synchronously in vaccinated pigs. Moreover, the granzyme b, nk-lysin, ifnγ, il4 and il10 mRNA levels in early skin-draining lymph nodes of immunized pigs were higher than those in pigs with non-irradiated cercariae infection. In addition, cytotoxicity-related genes in the mesenteric lymph nodes were significantly upregulated in vaccinated pigs in the acute infection. CONCLUSION/SIGNIFICANCE: Our results demonstrated that IFN-γ and IgG2 antibody production, as well as genes related to cytotoxicity are associated with the high level protection induced by UV-irradiated Schistosoma japonicum vaccine. These findings indicated that optimal vaccination against S. japonicum required the induction of IFN-γ, IgG2 antibody related to Th1 responses and cytotoxicity effect

Travel Dynamics Analysis and Intelligent Path Rectification Planning of a Roadheader on a Roadway

The tunneling work belongs to the group operation of semi-closed space, and the work is difficult with a high risk coefficient. It is an urgent requirement of coal mining to achieve unmanned and intelligent tunneling work. The path rectification planning of roadheaders is a necessary step before roadway cutting. In the traditional dynamic modeling analysis of roadhead tracks, problems such as compaction resistance, bulldozing resistance, steering resistance, tunnel dip angle, ditching, and obstacle-crossing capacity are not considered. In order to approximate the kinematic and dynamic parameters of a roadheader’s deviation correction under actual working conditions, this paper establishes kinematic and dynamic models of a roadheader’s path rectification at low speeds and under complex working conditions, and calculates the obstacle-crossing ability of roadheaders in the course of path rectification by modes based on roadway conditions, crawler resistance, and driving performance of the roadheader. Field experiments were carried out to verify the effectiveness of the dynamic model. The dynamic roadheader model was used in combination with actual working conditions of roadways in order to establish a roadway grid model. The grid model was simplified using rectifying influence degree and distance cost. The roadheader dynamic model and grid model were then used to propose a path rectification planning and tracking algorithm based on particle swarm optimization of the actual roadway conditions and roadheader driving performance. Finally, the effectiveness and superiority of the algorithm were verified using MATLAB simulation. The algorithm can provide strong technical guarantee for the intelligence of roadheader and unmanned mining. The results presented here can provide theoretical and technical support for the structural optimization and intelligent travel control of roadheaders

Comparison of Schistosoma mansoni Soluble Cercarial Antigens and Soluble Egg Antigens for Serodiagnosing Schistosome Infections

A Schistosoma mansoni cercarial antigen preparation (cercarial transformation fluid – SmCTF) was evaluated for detection of anti-schistosome antibodies in human sera in 4 collaborating laboratories. The performance of SmCTF was compared with that of S. mansoni egg antigens (SmSEA) in an indirect enzyme-immunoassay (ELISA) antigen assay, the latter being used routinely in 3 of the 4 participating laboratories to diagnose S. mansoni and S. haematobium infections. In the fourth laboratory the performance of SmCTF was compared with that of S. japonicum egg antigens (SjSEA) in ELISA for detection of anti-S. japonicum antibodies. In all 4 laboratories the results given by SmCTF in ELISA were very similar to those given by the antigen preparation routinely used in the respective laboratory to detect anti-schistosome antibodies in human infection sera. In so far as the ELISA results from SmCTF are thus so little different from those given by schistosome egg antigens and also cheaper to produce, the former is a potentially useful new diagnostic aid for schistosomiasis

Effects of virtual reality simulation on medical students’ learning and motivation in human parasitology instruction: a quasi-experimental study

Abstract Background Despite the proven effectiveness of simulation-based learning activities, its adoption in medical education remains limited, and the influence of simulation on student motivation, particularly subjective task values, is seldom explored. This study aimed to investigate the impact of a simulation-based learning activity on student learning and subjective task values in a medical morphology-related course of Human Parasitology. Methods A quasi-experimental study was conducted with 113 Chinese undergraduate medical students who participated in a Human Parasitology course during April to May 2022. Students were divided into two groups: Simulation Group (n = 55), where students used the simulation, and Lecture Group (n = 58), where students attended an online lecture. Students’ learning was measured prior to the intervention, immediately after the intervention, and three weeks later to assess knowledge retention. The subjective task values questionnaire was administered before and after the interventions. Data were analyzed using one-way ANCOVA and MANOVA. Results Students in the Simulation Group exhibited significantly higher knowledge gain compared to the Lecture Group [F (1,110) = 23.69, p < 0.01]. Additionally, the Simulation Group retained knowledge significantly better than the Lecture Group [F (1,101) = 10.05, p < 0.005]. Furthermore, students in the Simulation Group experienced a significant increase in subjective task values after the intervention [F (3, 52) = 3.57, p < 0.05, η p 2  = 0.17], while students in the Lecture Group reported a significant decrease in subjective task values [F (3, 55) = 2.96, p < 0.05, η p 2  = 0.14]. Conclusions Simulation-based learning not only leads to superior learning but also enhances students’ subjective task values. These findings offer valuable insights into designing effective simulation-based learning experiences in medical education and have significant practical implications for educators and medical professionals

Analysis of Vibration of Roadheader Rotary Table Based on Finite Element Method and Data from Underground Coalmine

The intense vibration of a roadheader rotary table damages the cutting system of the roadheader and reduces the efficiency. This paper analyzes the vibration of a rotary table by combining the finite element model with tested data from an underground coalmine. First, the force of the rotary table during the cutting procedure was analyzed, and the finite element model was built using Pro/E and ADAMS. The tested data were then imported into the model after selection, procession, and combination were conducted. Next, the six lowest-order parameters of the rotary table were calculated. A vibration analysis of the rotary table under certain working conditions was conducted, and the results were compared with those from a modal experiment using a single-point excitation method. According to the comparison between the simulation result and experiments, it is clear that this method is both reasonable and feasible. And it could supplement the theoretical foundation of the analysis of other roadheader components, providing reference for the improvement of the structure and dynamic properties of a roadheader. In addition, other vibration components of a roadheader such as the cutting head and the cutting arm could also be analyzed through the proposed method, with very reliable precision

Analysis of Vibration of Roadheader Rotary Table Based on Finite Element Method and Data from Underground Coalmine

The intense vibration of a roadheader rotary table damages the cutting system of the roadheader and reduces the efficiency. This paper analyzes the vibration of a rotary table by combining the finite element model with tested data from an underground coalmine. First, the force of the rotary table during the cutting procedure was analyzed, and the finite element model was built using Pro/E and ADAMS. The tested data were then imported into the model after selection, procession, and combination were conducted. Next, the six lowest-order parameters of the rotary table were calculated. A vibration analysis of the rotary table under certain working conditions was conducted, and the results were compared with those from a modal experiment using a single-point excitation method. According to the comparison between the simulation result and experiments, it is clear that this method is both reasonable and feasible. And it could supplement the theoretical foundation of the analysis of other roadheader components, providing reference for the improvement of the structure and dynamic properties of a roadheader. In addition, other vibration components of a roadheader such as the cutting head and the cutting arm could also be analyzed through the proposed method, with very reliable precision