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Helminth infections are a major public health problem as they can cause long-term chronic infections in their hosts for which there is no effective vaccine. During the long-term interaction between helminths and their hosts, helminth-derived extracellular vesicles (EVs) can participate in host immunomodulatory processes by secreting bioactive molecules (BMAs). Growing data suggests that microRNAs (miRNAs) in helminth EVs have a significant impact on the host’s immune system. The let-7 family is highly conserved among helminth EVs and highly homologous in the host, and its function in host–parasite crosstalk may reflect active selection for compatibility with the host miRNA machinery. In-depth studies targeting this aspect may better elucidate the mechanism of parasite-host interactions. Hence, this review summarizes the current studies on the cross-species involvement of helminth EV-derived let-7 in host immune regulation and discusses the barriers to related research and potential applications of helminth EVs.

Babesiosis is an emerging and re-emerging zoonosis that is prevalent worldwide, caused by over 100 Babesia species. These intracellular parasites efficiently invade host red bloods cells, replicate rapidly, and exit the infected cells to cause clinical symptoms. However, the underlying mechanisms of regulating this asexual stage is largely unknown. Here, we generated a chromosome-level reference assembly of a novel Babesia species, Babesia xinjiangensis . Using single-copy orthologous genes, we confirmed its phylogenetic relationships with other apicomplexan parasites and estimated its speciation time. We identified species-specific gene families and core gene families that could be responsible for species speciation and immune evasion. Furthermore, we also used a single-cell RNA-sequencing (scRNA-seq) protocol to uncover hidden transcriptional variations in the asexual stages of this unicellular Babesia parasite and its cell-to-cell heterogeneity. We inferred the replication cycle and performed a pseudotime analysis to speculate the gene expression profiles. Although the peak expression times of most epigenetic markers and transcription factors were confined to specific phases, BxAP2-M2 (GWHPERCV002055) is constantly expressed during asexual development progression. Genetic analyses revealed that BxAP2-M2 directly or indirectly regulates the expression of rhoptry proteins and membrane proteins, which may play critical roles in the parasite’s invasion of red blood cells and the merozoite morphology. Our findings provide valuable markers of asexual replication, including some that are specific to Babesia gametocytes, and regulators specific to distinct cell-cycle phases.

The BET (bromodomain and extraterminal domain) family of proteins, particularly BRD4 (bromodomain-containing protein 4), plays a crucial role in transcription regulation and epigenetic mechanisms, impacting key cellular processes such as proliferation, differentiation, and the DNA damage response. BRD4, the most studied member of this family, binds to acetylated lysines on both histones and non-histone proteins, thereby regulating gene expression and influencing diverse cellular functions such as the cell cycle, tumorigenesis, and immune responses to viral infections. Given BRD4’s involvement in these fundamental processes, it is implicated in various diseases, including cancer and inflammation, making it a promising target for therapeutic development. This review comprehensively explores the roles of the BET family in gene transcription, DNA damage response, and viral infection, discussing the potential of targeted small-molecule compounds and highlighting BET proteins as promising candidates for anticancer therapy.

Background SET domain-containing histone lysine methyltransferases (HKMTs) and JmjC domain-containing histone demethylases (JHDMs) are essential for maintaining dynamic changes in histone methylation across parasite development and infection. However, information on the HKMTs and JHDMs in human pathogenic piroplasms, such as Babesia duncani and Babesia microti , and in veterinary important pathogens, including Babesia bigemina , Babesia bovis , Theileria annulata and Theileria parva , is limited. Results A total of 38 putative KMTs and eight JHDMs were identified using a comparative genomics approach. Phylogenetic analysis revealed that the putative KMTs can be divided into eight subgroups, while the JHDMs belong to the JARID subfamily, except for BdJmjC1 (BdWA1_000016) and TpJmjC1 (Tp Muguga_02g00471) which cluster with JmjC domain only subfamily members. The motifs of SET and JmjC domains are highly conserved among piroplasm species. Interspecies collinearity analysis provided insight into the evolutionary duplication events of some SET domain and JmjC domain gene families. Moreover, relative gene expression analysis by RT‒qPCR demonstrated that the putative KMT and JHDM gene families were differentially expressed in different intraerythrocytic developmental stages of B. duncani , suggesting their role in Apicomplexa parasite development. Conclusions Our study provides a theoretical foundation and guidance for understanding the basic characteristics of several important piroplasm KMT and JHDM families and their biological roles in parasite differentiation.

Background Extracellular vesicles (EVs) play a pivotal role in host-parasite interactions, particularly in facilitating parasite pathogenesis and immune modulation, and are crucial mediators of intercellular communication. Theileria annulata , an apicomplexan parasite, induces severe alterations in host cells, promoting uncontrolled proliferation, resistance to apoptosis, and immune evasion. Although EVs contribute to these processes, the proteins and small RNA cargo involved in T. annulata infection remain incompletely characterized. In particular, little is known about EV profiles in infections caused by drug-resistant field strains. Methods In this study, we conducted systematic proteomic and small RNA profiling of EVs derived from naturally occurring buparvaquone-resistant T. annulata (Xinjiang Kashi strain) infected and uninfected bovine sera to investigate infection-induced alterations. Additionally, EVs were isolated from T. annulata -infected bovine immune cells to determine the protein and microRNA (miRNA) compositions of EVs secreted by specific immune cell types. Label-free liquid chromatography–tandem mass spectrometry proteomics and small RNA sequencing were employed to identify EV-associated proteins and miRNAs, followed by functional enrichment analysis to explore key host-parasite regulatory pathways. Results Our analysis identified 2580 proteins and 6635 miRNAs in EVs derived from T. annulata -infected bovine serum and immune cell types, many of which are implicated in parasite development, host invasion, and immune modulation. Significant alterations were observed in the EV cargo from infected sera, including enrichment of vesicular proteins and miRNAs associated with immune regulation, metabolic reprogramming, and host–pathogen interactions. Furthermore, functional enrichment analyses highlighted key pathways such as ECM-receptor interactions, oxidative phosphorylation, and proton transport, underscoring the role of EVs in host immune modulation. Supplementary analysis of EVs from infected immune cells provided further insights into the cell type-specific contributions. Conclusions This study comprehensively characterized the infection-induced changes in serum-derived EVs associated with a naturally occurring buparvaquone-resistant T. annulata infection. It offers novel insights into how T. annulata exploits EVs to manipulate host responses. The identification of unique EV-associated proteins and miRNAs highlights their potential as biomarkers and therapeutic targets for Theileria infections. These findings contribute to a deeper understanding of host-parasite interactions and lay the foundation for future investigations into EV-mediated pathogenesis and immune evasion. Graphical abstract

Vaccination remains the sole effective strategy for combating Japanese encephalitis (JE). Both inactivated and live attenuated vaccines exhibit robust immunogenicity. However, the production of these conventional vaccine modalities necessitates extensive cultivation of the pathogen, incurring substantial costs and presenting significant biosafety risks. Moreover, the administration of live pathogens poses potential hazards for individuals or animals with compromised immune systems or other health vulnerabilities. Subsequently, ongoing research endeavors are focused on the development of next-generation JE vaccines utilizing nanoparticle (NP) platforms. This systematic review seeks to aggregate the research findings pertaining to NP-based vaccine development against JE. A thorough literature search was conducted across established English-language databases for research articles on JE NP vaccine development published between 2000 and 2023. A total of twenty-eight published studies were selected for detailed analysis in this review. Of these, 16 studies (57.14%) concentrated on virus-like particles (VLPs) employing various structural proteins. Other approaches, including sub-viral particles (SVPs), biopolymers, and both synthetic and inorganic NP platforms, were utilized to a lesser extent. The results of these investigations indicated that, despite variations in the usage of adjuvants, dosages, NP types, antigenic proteins, and animal models employed across different studies, the candidate NP vaccines developed were capable of eliciting enhanced humoral and cellular adaptive immune responses, providing effective protection (70–100%) for immunized mice against lethal challenges posed by virulent Japanese encephalitis virus (JEV). In conclusion, prospective next-generation JE vaccines for humans and animals may emerge from these candidate formulations following further evaluation in subsequent vaccine development phases.

Background Human babesiosis, caused by parasites of the genus Babesia , is an emerging and re-emerging tick-borne disease that is mainly transmitted by tick bites and infected blood transfusion. Babesia duncani has caused majority of human babesiosis in Canada; however, limited data are available to correlate its genomic information and biological features. Results We generated a B. duncani reference genome using Oxford Nanopore Technology (ONT) and Illumina sequencing technology and uncovered its biological features and phylogenetic relationship with other Apicomplexa parasites. Phylogenetic analyses revealed that B. duncani form a clade distinct from B. microti , Babesia spp. infective to bovine and ovine species, and Theileria spp. infective to bovines. We identified the largest species-specific gene family that could be applied as diagnostic markers for this pathogen. In addition, two gene families show signals of significant expansion and several genes that present signatures of positive selection in B. duncani , suggesting their possible roles in the capability of this parasite to infect humans or tick vectors. Conclusions Using ONT sequencing and Illumina sequencing technologies, we provide the first B. duncani reference genome and confirm that B. duncani forms a phylogenetically distinct clade from other Piroplasm parasites. Comparative genomic analyses show that two gene families are significantly expanded in B. duncani and may play important roles in host cell invasion and virulence of B. duncani . Our study provides basic information for further exploring B. duncani features, such as host-parasite and tick-parasite interactions.

Babesiosis is a tick-borne disease with global impact caused by parasites of the phylum Apicomplexa, genus Babesia. Typically, acute bovine babesiosis (BB) is characterized by fever, anemia, hemoglobinuria, and high mortality. Surviving animals remain persistently infected and become reservoirs for parasite transmission. Bovids in China can be infected by one or more Babesia species endemic to the country, including B. bovis , B. bigemina , B. orientalis , B. ovata , B. major , B. motasi , B. U sp. Kashi and B. venatorum . The latter may pose a zoonotic risk. Occurrence of this wide diversity of Babesia species in China may be due to a combination of favorable ecological factors, such as the presence of multiple tick vectors, including Rhipicephalus and Hyalomma , the coexistence of susceptible bovid species, such as domestic cattle, yaks, and water buffalo, and the lack of efficient measures of tick control. BB is currently widespread in several regions of the country and a limiting factor for cattle production. While some areas appear to have enzootic stability, others have considerable cattle mortality. Research is needed to devise solutions to the challenges posed by uncontrolled BB. Critical research gaps include risk assessment for cattle residing in endemic areas, understanding factors involved in endemic stability, evaluation of parasite diversity and pathogenicity of regional Babesia species, and estimation of whether and how BB should be controlled in China. Research should allow the design of comprehensive interventions to improve cattle production, diminish the risk of human infections, and increase the availability of affordable animal protein for human consumption in China and worldwide. In this review, we describe the current state of BB with reference to the diversity of hosts, vectors, and parasite species in China. We also discuss the unique risks and knowledge gaps that should be taken into consideration for future Babesia research and control strategies.

BACKGROUND: Anaplasmosis is caused by obligate intracellular bacteria in the genus Anaplasma. These bacterial pathogens are transmitted by ticks and impact both human and animal health. This study was conducted to determine the prevalence and molecular characterization of Anaplasma spp. in ruminants sampled in Xinjiang, northwest China. METHODS: A survey was performed in August 2012 in rural areas of six counties in Xinjiang province. A total of 250 blood samples from ruminants were collected and tested for the presence of Anaplasma spp. by PCR. Positive samples were genetically characterized based on the 16S rRNA and msp4 genes. RESULTS: The results showed a high prevalence of Anaplasma spp. in ruminants, with at least three different Anaplasma species detected (A. phagocytophilum, A. bovis and A. ovis). The mean prevalence of single infection with each species was 17.6% (A. phagocytophilum), 4.8% (A. bovis) and 40.5% (A. ovis). Coinfection occurred in 20 (8.0%) animals. Phylogenetic analysis of the 16S rRNA gene of A. bovis and A. phagocytophilum revealed a higher degree of genetic diversity for the latter. The results for A. ovis showed genotypic variation among geographic regions in China. In addition, a closely related isolate to the canine pathogen A. platys was identified in ruminants. CONCLUSIONS: This survey revealed a high prevalence of Anaplasma sp. infections in sheep and cattle in the northwestern border regions of China, indicating the potential risk of transboundary disease.