Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis

BACKGROUND: Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii. The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii. METHODS: Using bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines. RESULTS: TgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection. CONCLUSIONS: T. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines

Immunogenicity of a Virus-Like-Particle Vaccine Containing Multiple Antigenic Epitopes of Toxoplasma gondii Against Acute and Chronic Toxoplasmosis in Mice

There is no effective protective vaccine against human toxoplasmosis, which is a potential threat to nearly a third of the world population. Vaccines based on virus-like particles (VLPs) have been highly successful in humans for many years, but have rarely been applied against Toxoplasma gondii infection. In this study, we inserted a B cell epitope (SAG182−102 or SAG1301−320), a CD8+ cell epitope (HF10 or ROP7), and a CD4+ cell epitope (AS15) of T. gondii into a truncated HBcΔ(amino acids1–149) particle to construct four chimeric VLP vaccine formulations, i.e., HBcΔH82, HBcΔH301, HBcΔ R82, and HBcΔ R301. When these chimeric HBc particles were expressed in Escherichia coli, they showed icosahedral morphology similar to that of the original VLPs and were evaluated as vaccine formulations against acute and chronic toxoplasmosis in a mouse model (BALB/c mice (H-2d). All these chimeric HBc VLPs induced strong humoral and cellular immune responses with high IgG antibody titers and interferon(IFN)-γ production. Only the mice immunized with HBcΔH82 showed prolonged survival time (15.6 ± 3.8 vs. 5.6 ± 0.8 days) against acute infection with RH tachyzoites and decrease in brain parasite load (1,454 ± 239 vs. 2,091 ± 263) against chronic infection with Prugniuad cysts, as compared to the findings for the control group. These findings suggest that HBc VLPs would act as an effective carrier for delivering effective multiple antigenic epitopes and would be beneficial for developing a safe and long-acting vaccine against toxoplasmosis

Solar Ring Mission: Building a Panorama of the Sun and Inner-heliosphere

Solar Ring (SOR) is a proposed space science mission to monitor and study the Sun and inner heliosphere from a full 360{\deg} perspective in the ecliptic plane. It will deploy three 120{\deg}-separated spacecraft on the 1-AU orbit. The first spacecraft, S1, locates 30{\deg} upstream of the Earth, the second, S2, 90{\deg} downstream, and the third, S3, completes the configuration. This design with necessary science instruments, e.g., the Doppler-velocity and vector magnetic field imager, wide-angle coronagraph, and in-situ instruments, will allow us to establish many unprecedented capabilities: (1) provide simultaneous Doppler-velocity observations of the whole solar surface to understand the deep interior, (2) provide vector magnetograms of the whole photosphere - the inner boundary of the solar atmosphere and heliosphere, (3) provide the information of the whole lifetime evolution of solar featured structures, and (4) provide the whole view of solar transients and space weather in the inner heliosphere. With these capabilities, Solar Ring mission aims to address outstanding questions about the origin of solar cycle, the origin of solar eruptions and the origin of extreme space weather events. The successful accomplishment of the mission will construct a panorama of the Sun and inner-heliosphere, and therefore advance our understanding of the star and the space environment that holds our life.Comment: 41 pages, 6 figures, 1 table, to be published in Advances in Space Researc

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.0443

Multi-Label Vulnerability Detection of Smart Contracts Based on Bi-LSTM and Attention Mechanism

Smart contracts are decentralized applications running on blockchain platforms and have been widely used in a variety of scenarios in recent years. However, frequent smart contract security incidents have focused more and more attention on their security and reliability, and smart contract vulnerability detection has become an urgent problem in blockchain security. Most of the existing methods rely on fixed rules defined by experts, which have the disadvantages of single detection type, poor scalability, and high false alarm rate. To solve the above problems, this paper proposes a method that combines Bi-LSTM and an attention mechanism for multiple vulnerability detection of smart contract opcodes. First, we preprocessed the data to convert the opcodes into a feature matrix suitable as the input of the neural network and then used the Bi-LSTM model based on the attention mechanism to classify smart contracts with multiple labels. The experimental results show that the model can detect multiple vulnerabilities at the same time, and all evaluation indicators exceeded 85%, which proves the effectiveness of the method proposed in this paper for multiple vulnerability detection tasks in smart contracts

Multi-Label Vulnerability Detection of Smart Contracts Based on Bi-LSTM and Attention Mechanism

Smart contracts are decentralized applications running on blockchain platforms and have been widely used in a variety of scenarios in recent years. However, frequent smart contract security incidents have focused more and more attention on their security and reliability, and smart contract vulnerability detection has become an urgent problem in blockchain security. Most of the existing methods rely on fixed rules defined by experts, which have the disadvantages of single detection type, poor scalability, and high false alarm rate. To solve the above problems, this paper proposes a method that combines Bi-LSTM and an attention mechanism for multiple vulnerability detection of smart contract opcodes. First, we preprocessed the data to convert the opcodes into a feature matrix suitable as the input of the neural network and then used the Bi-LSTM model based on the attention mechanism to classify smart contracts with multiple labels. The experimental results show that the model can detect multiple vulnerabilities at the same time, and all evaluation indicators exceeded 85%, which proves the effectiveness of the method proposed in this paper for multiple vulnerability detection tasks in smart contracts

Teaching human parasitology in China

Abstract China has approximately one-fifth of the world’s population. Despite the recent success in controlling major parasitic diseases, parasitic diseases remain a significant human health problem in China. Hence, the discipline of human parasitology is considered as a core subject for undergraduate and postgraduate students of the medical sciences. We consider the teaching of human parasitology to be fundamental to the training of medical students, to the continued research on parasitic diseases, and to the prevention and control of human parasitic diseases. Here, we have summarized the distribution of educational institutions in China, particularly those that teach parasitology. In addition, we have described some existing parasitology courses in detail as well as the teaching methods used for different types of medical students. Finally, we have discussed the current problems in and reforms to human parasitology education. Our study indicates that 304 regular higher education institutions in China offer medical or related education. More than 70 universities have an independent department of parasitology that offers approximately 10 different parasitology courses. In addition, six universities in China have established excellence-building courses in human parasitology.</p

Immunization with a DNA vaccine encoding Toxoplasma gondii Superoxide dismutase (TgSOD) induces partial immune protection against acute toxoplasmosis in BALB/c mice

Abstract Background Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects all warm-blooded animals including humans and causes toxoplasmosis. An effective vaccine could be an ideal choice for preventing and controlling toxoplasmosis. T. gondii Superoxide dismutase (TgSOD) might participate in affecting the intracellular growth of both bradyzoite and tachyzoite forms. In the present study, the TgSOD gene was used to construct a DNA vaccine (pEGFP-SOD). Methods TgSOD gene was amplified and inserted into eukaryotic vector pEGFP-C1 and formed the DNA vaccine pEGFP-SOD. Then the BALB/c mice were immunized intramuscularly with the DNA vaccine and those injected with pEGFP-C1, PBS or nothing were treated as controls. Four weeks after the last immunization, all mouse groups followed by challenging intraperitoneally with tachyzoites of T. gondii ME49 strain. Results Results showed higher levels of total IgG, IgG2α in the sera and interferon gamma (IFN-γ) in the splenocytes from pEGFP-SOD inoculated mice than those unvaccinated, or inoculated with either empty plasmid vector or PBS. The proportions of CD4+ T cells and CD8+ T cells in the spleen from pEGFP-SOD inoculated mice were significantly (p < 0.05) increased compared to control groups. In addition, the survival time of mice immunized with pEGFP-SOD was significantly prolonged as compared to the controls (p < 0.05) although all the mice died. Conclusion The present study revealed that the DNA vaccine triggered strong humoral and cellular immune responses, and aroused partial protective immunity against acute T. gondii infection in BALB/c mice. The collective data suggests the SOD may be a potential vaccine candidate for further development

<it>Toxoplasma gondii </it>infection in humans in China

Abstract Toxoplasmosis is a zoonotic infection of humans and animals, caused by the opportunistic protozoan Toxoplasma gondii, a parasite belonging to the phylum Apicomplexa. Infection in pregnant women may lead to abortion, stillbirth or other serious consequences in newborns. Infection in immunocompromised patients can be fatal if not treated. On average, one third of people are chronically infected worldwide. Although very limited information from China has been published in the English journals, T. gondii infection is actually a significant human health problem in China. In the present article, we reviewed the clinical features, transmission, prevalence of T. gondii infection in humans in China, and summarized genetic characterizations of reported T. gondii isolates. Educating the public about the risks associated with unhealthy food and life style habits, tracking serological examinations to special populations, and measures to strengthen food and occupational safety are discussed.</p