Important progress has been made in understanding how immunity is elicited against Toxoplasma gondii – a complex pathogen with multiple mechanisms of immune evasion. Many vaccine candidates have been ...tested using various strategies in animal models. However, none of these strategies has delivered as yet, and important challenges remain in the development of vaccines that can eliminate the tissue cysts and/or fully block vertical transmission. In this review, we provide an overview of the current understanding of the host immune response to T. gondii infection and summarize the key limitations for the development of an effective, safe, and durable toxoplasmosis vaccine. We also discuss how the successes and failures in developing and testing vaccine candidates have provided a roadmap for future vaccine development.
There is a compelling need to develop a safe and effective toxoplasmosis vaccine.
Successful vaccination of domestic cats is the key step in reducing T. gondii transmission to humans and food-producing animals.
An effective toxoplasmosis vaccine must be able to induce both humoral and cellular immune responses, directed against multiple different proteins, at different stages of the parasite life cycle.
Live attenuated T. gondii strains offer good protection against toxoplasmosis, but the possibility of reversion to the virulent type remains possible.
There is a need to identify more immunogenic antigens, adjuvants, and antigen-delivery systems together with defining robust immunocorrelates of protection.
Having a standardized protocol for assessment of vaccine efficacy can facilitate the synergy between the results obtained by various research groups.
‘Omics’ technologies have revolutionized our understanding of the pathophysiology of toxoplasmosis, paving the way for development of a safe and effective vaccine.
Sexual development in Toxoplasma gondii is a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms ...governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro.
Fluorescent nanocomposite gels have attracted increasing attention due to their excellent optical properties, as well as enhanced mechanical strength originating from the nanoparticles. At present, ...two‐step methods are usually employed, where fluorescent nanoparticles are firstly prepared, followed by mixing with gel precursor to achieve the final products after gelation, which suffer from the disadvantages of a tedious and time‐consuming process. Thus, the development of a facile strategy is highly desirable, which still remains an obstacle. Herein, a new one‐pot synthesis method towards robust fluorescent nanocomposite gels via frontal polymerization (FP) is proposed, where small molecular precursors (citric acid (CA) and urea, or L‐cysteine) and gel precursor (vinyl monomers) are mixed together as co‐reactants. During the FP process, a lot of heat release gives rise to the generation of carbonized polymer dots (CPDs). Thus, companying with the propagating of the polymerization, the production of fluorescent CPDs/gel composite is completed. In addition, as a nanofiller, CPDs dramatically enhance the mechanical property of the CPDs/gel composite. This work proposes a new fast and efficient one‐pot strategy for the production of CPDs/gel composite, which will guide the development of high‐performance polymer nanocomposites through an in situ synchronous reaction fashion.
A one‐pot synthesis route to fabricate robust fluorescent carbonized polymer dots (CPDs)/gel composite via frontal polymerization (FP) is developed, which can effectively utilize the heat release during the FP process, allowing the formation of gels and generation of CPDs simultaneously. The as‐prepared CPDs not only bring fluorescent properties, but also greatly enhance the mechanical strength of the gel.
Monodispersed microspheres play a major role in optical science and engineering, providing ideal building blocks for structural color materials. However, the method toward high solid content (HSC) ...monodispersed microspheres has remained a key hurdle. Herein, a facile access to harvest monodispersed microspheres based on the emulsion polymerization mechanism is demonstrated, where anionic and nonionic surfactants are employed to achieve the electrostatic and steric dual‐stabilization balance in a synergistic manner. Monodispersed poly(styrene‐butyl acrylate‐methacrylic acid) colloidal latex with 55 wt% HSC is achieved, which shows an enhanced self‐assembly efficiency of 280% compared with the low solid content (10 wt%) latex. In addition, Ag‐coated colloidal photonic crystal (Ag@CPC) coating with near‐zero refractive index is achieved, presenting the characteristics of metamaterials. And an 11‐fold photoluminescence emission enhancement of CdSe@ZnS quantum dots is realized by the Ag@CPC metamaterial coating. Taking advantage of high assembly efficiency, easily large‐scale film‐forming of the 55 wt% HSC microspheres latex, robust Ag@CPC metamaterial coatings could be easily produced for passive cooling. The coating demonstrates excellent thermal insulation performance with theoretical cooling power of 30.4 W m−2, providing practical significance for scalable CPC architecture coatings in passive cooling.
A dual‐surfactants‐mediated emulsion polymerization mechanism is proposed, where anionic and nonionic surfactants are employed due to their synergistic effect to guarantee the electrostatic and steric dual‐stabilization balance. Thus, 55 wt% high solid content poly(styrene‐butyl acrylate‐methacrylic acid) monodispersed colloidal latex is achieved, which can be used to construct metamaterials toward photoluminescence enhancement and passive cooling coatings.
Toxoplasma gondii, a significant public health risk, is able to infect almost all warm-blooded animals including humans, and it results in economic losses in production animals. In the last three ...years, a large number of vaccination experiments have been performed to control T. gondii infection, with the target of limiting the acute infection and reducing or eliminating tissue cysts in the intermediate hosts. In this paper, we summarize the latest results of the veterinary vaccines against T. gondii infection since 2013. Immunization with live-attenuated whole organisms of non-reverting mutants has been shown to induce remarkably potent immune responses associated with control of acute and chronic toxoplasmosis. The non-cyst-forming mutants are promising new tools for the development of veterinary vaccines against T. gondii infection.
Transition metal oxides or (oxy)hydroxides have been intensively investigated as promising electrocatalysts for energy and environmental applications. Oxygen in the lattice was reported recently to ...actively participate in surface reactions. Herein, we report a sacrificial template-directed approach to synthesize Mo-doped NiFe (oxy)hydroxide with modulated oxygen activity as an enhanced electrocatalyst towards oxygen evolution reaction (OER). The obtained MoNiFe (oxy)hydroxide displays a high mass activity of 1910 A/g
at the overpotential of 300 mV. The combination of density functional theory calculations and advanced spectroscopy techniques suggests that the Mo dopant upshifts the O 2p band and weakens the metal-oxygen bond of NiFe (oxy)hydroxide, facilitating oxygen vacancy formation and shifting the reaction pathway for OER. Our results provide critical insights into the role of lattice oxygen in determining the activity of (oxy)hydroxides and demonstrate tuning oxygen activity as a promising approach for constructing highly active electrocatalysts.
Abstract
The redox center of transition metal oxides and hydroxides is generally considered to be the metal site. Interestingly, proton and oxygen in the lattice recently are found to be actively ...involved in the catalytic reactions, and critically determine the reactivity. Herein, taking glycerol electrooxidation reaction as the model reaction, we reveal systematically the impact of proton and oxygen anion (de)intercalation processes on the elementary steps. Combining density functional theory calculations and advanced spectroscopy techniques, we find that doping Co into Ni-hydroxide promotes the deintercalation of proton and oxygen anion from the catalyst surface. The oxygen vacancies formed in NiCo hydroxide during glycerol electrooxidation reaction increase
d
-band filling on Co sites, facilitating the charge transfer from catalyst surface to cleaved molecules during the 2
nd
C-C bond cleavage. Consequently, NiCo hydroxide exhibits enhanced glycerol electrooxidation activity, with a current density of 100 mA/cm
2
at 1.35 V and a formate selectivity of 94.3%.
Minks and brown rats are reservoir hosts for many endoparasites including those of the genus Trichinella, a group of parasite nematodes with a worldwide distribution. However, little is known about ...the prevalence of Trichinella sp. infection in the American mink (Neovison vison) and rats (Rattus norvegicus) in China. Therefore, we aimed to examine the prevalence of Trichinella sp. infection in farmed minks in Weihai city, Shandong province, China and infer the possible route for Trichinella transmission to farmed American minks. In total, 289 muscle samples from minks and 102 carcasses of rats were collected from Weihai City. The appearance of Trichinella sp. was examined using the pooled artificial HCl‐pepsin digestion method. The results showed that muscle larvae were detected in 20 of 289 minks (6.92%) and 2 of 102 synanthropic rats (1.96%). The larval density of Trichinella sp. in mink samples ranged from 0.025 to 0.815 larvae per gram (lpg), while the average larval burden in rats was 0.17 lpg. The isolates derived from minks and rats were identified at the species level using multiplex polymerase chain reaction (PCR), which revealed that the size of the two PCR products matched that of T. spiralis at 173 bp. Furthermore, sequence analysis showed 100% identity of the 5S rDNA inter‐gene spacer regions of the two isolates to that of T. spiralis. This study presents a novel report of T. spiralis‐mediated infection in minks and synanthropic rats in China. We highlight the vulnerability of farmed minks to Trichinella infection through exposure to synanthropic rats, which may raise a public health concern of potential zoonotic risks for domestic animals.
Adopting inorganic solid electrolytes (ISEs) is a promising approach to assemble batteries using Li metal anodes because of their superior Li-ion conductivity and high mechanical strength. This ...approach greatly improves the energy density and the safety of batteries. However, lithium dendrites still can pierce the bare ISE because of inhomogeneous current distributions at interfaces, leading to serious short circuits. This work proposes to reduce the interfacial resistance and prevent lithium dendrite growth simultaneously through
in situ
formation of interlayers enabled by a conversion reaction of MoS
2
layers coated on a bare Li
6.5
La
3
Zr
1.5
Ta
0.5
O
12
(LLZO) pellet. The interfacial resistance is reduced to only 14 Ω cm
2
, with the overpotential decreasing notably. The critical current density of cells is improved from 0.7 mA cm
−2
to 2.2 mA cm
−2
. Furthermore, short circuits are significantly suppressed above the critical current density with the potential diverging quickly. The cell can be recovered to some extent by applying an inverse potential for a short time. The comparison between XPS and XAS measurements reveals that the nanoscale thin MoS
2
layer in contact with the Li anode can be converted into an interlayer composed of Mo and Li
2
S through the conversion reaction. The sluggish kinetics of the conversion reaction resulting from the poor electronic conductivity makes the
in situ
-formed interlayer kinetically stable, which can hinder further reaction of MoS
2
with Li effectively. Moreover, the
in situ
reaction could suppress the local tip electric field effect efficiently and make the current distribution more even. This study provides a new strategy to optimize the interface of anodes by screening for more candidates which undergo a conversion reaction.
A DNA-encoded library is a collection of small molecules covalently linked to DNA that has unique information about the identity and the structure of each library member. A DNA-encoded chemical ...library (DEL) is broadly adopted by major pharmaceutical companies and used in numerous drug discovery programs. The application of the DEL technology is advantageous at the initial period of drug discovery because of reduced cost, time, and storage space for the identification of target compounds. The key points for the construction of DELs comprise the development and the selection of the encoding methods, transfer of routine chemical reaction from off-DNA to on-DNA, and exploration of new chemical reactions on DNA. The limitations in the chemical space and the diversity of DEL were reduced gradually by using novel DNA-compatible reactions based on the formation and the cleavage of various bonds. Here, we summarized a series of novel DNA-compatible chemistry reactions for DEL building blocks and analysed the druggability of screened hit molecules
via
DELs in the past five years.
We summarize a series of novel DNA-compatible chemistry reactions for DNA-encoded chemical library (DEL) building blocks and analyse the druggability of screened hit molecules
via
DELs in the past five years.
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