Liang Lu

Parasites enhance their fitness by manipulating host dispersal. However, the strategies used by ectoparasites to influence host movement and the underlying mechanisms remain poorly understood. Here, we show that ectoparasites alter metabolic activity in specific brain regions of mice, with evidence pointing to a potential role for microglial activation in the prefrontal cortex. This activation appears to contribute to synaptic changes and altered neuronal differentiation, particularly in GABAergic neurons. Consequently, exploratory behavior decreases—an effect likely mediated through the skin–brain axis. In both indoor and field experiments with striped hamsters, ectoparasites reduce host exploration and modify their dispersal patterns. This behavioral shift ultimately restricts the host’s distribution, enabling parasites to avoid environmental pressures. Our findings reveal that ectoparasites limit host dispersal to improve their own fitness, offering key insights for parasite control strategies that promote health and preserve ecological stability within the One Health framework.

Introduction: The striped hamster, often parasitized by ectoparasites in nature, is an ideal model for studying host-ectoparasite molecular interactions. Investigating the response to ectoparasites under laboratory conditions helps elucidate the mechanism of host adaptations to ectoparasite pressure.Methods: Using transcriptome sequencing, we analyzed gene expression in striped hamsters after short-term (3 days) and long-term (28 days) flea (Xenopsylla cheopis) parasitism. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were pinpointed using protein-protein interaction (PPI) network analysis and the MCODE in Cytoscape. Gene Set Enrichment Analysis (GSEA) was used to further clarify the functional pathways of these hub genes. Validation of DEGs was performed via RT-qPCR. Additionally, the concentrations of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined using specific enzyme-linked immunosorbent assay (ELISA) detection kits for hamsters.Results: GO analysis revealed that during early parasitism, hosts primarily responded to the ectoparasites by adjusting the expression of genes related to metabolic functions. As parasitism persisted, the immune response became prominent, activating various immune pathways against ectoparasites. KEGG analysis confirmed the ongoing roles of metabolism and immunity. Notably, the chemical carcinogenesis - reactive oxygen species pathway was upregulated during flea parasitism, with downregulation of hub genes ATP5MC1 and ATP5MC2, highlighting the importance of mitochondrial function in oxidative stress. ELISA findings revealed that on day 3, flea parasitism groups showed elevated ROS expression and reduced SOD and CAT levels compared to the control group. By day 28, only SOD expression showed a significant decrease in both parasitism groups.Conclusion: This study uncovered the dynamic changes in metabolism and immune responses of striped hamsters parasitized by Xenopsylla cheopis. Hosts adjust their physiological and immune states to optimize survival strategies during different ectoparasite stages, enhancing our understanding of host-ectoparasite interactions. This also paves the way for further research into how hosts regulate complex biological processes in response to ectoparasite challenges.

Background: Studies have reported the adverse effects of cold events on influenza. However, the role of critical factors, such as characteristics of cold spells, and regional variations remain unresolved. Objective: We aimed to systematically evaluate the association between cold spells and influenza incidence in mainland China. Methods: This time series analysis used surveillance data of daily influenza from 325 sites in China in the 2014‐2019 period. A total of 15 definitions of cold spells were adopted based on combinations of temperature thresholds and days of duration. A distributed lag linear model was used to estimate the short-term effects of cold spells on influenza incidence during the cool seasons (November to March), and we further explored the potential impact of cold spell characteristics (ie, intensity, duration, and timing during the season) on the estimated associations. Meta-regressions were used to evaluate the modification effect of city-level socioeconomic indicators. Results: The overall effect of cold spells on influenza incidence increased with the temperature threshold used to define cold spells, whereas the added effects were generally small and not statistically significant. The relative risk of influenza-associated with cold spells was 3.35 (95% CI 2.89‐3.88), and the estimated effects were stronger during the middle period of cool seasons. The health effects of cold spells varied geographically and residents in Jiangnan region were vulnerable groups (relative risk 7.36, 95% CI 5.44‐9.95). The overall effects of cold spells were positively correlated with the urban population density, population size, gross domestic product per capita, and urbanization rate, indicating a sterner response to cold spells in metropolises. Conclusions: Cold spells create a substantial health burden on seasonal influenza in China. Findings on regional and socioeconomic differences in the health effects of cold spells on seasonal influenza may be useful in formulating region-specific public health policies to address the hazardous effects of cold spells.

Background: Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites. Methods: RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein–protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results: A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable. Conclusions: Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites. Graphical

Plague, as an ancient zoonotic disease caused by Yersinia pestis, has brought great disasters. The natural plague focus of Marmota himalayana in the Qinghai-Tibet Plateau is the largest, which has been constantly active and the leading source of human plague in China for decades. Understanding the population genetics of M. himalayana and relating that information to the biogeographic distribution of Yersinia pestis and plague outbreaks are greatly beneficial for the knowledge of plague spillover and arecrucial for pandemic prevention. In the present research, we assessed the population genetics of M. himalayana. We carried out a comparative study of plague outbreaks and the population genetics of M. himalayana on the Qinghai-Tibet Plateau. We found that M. himalayana populations are divided into two main clusters located in the south and north of the Qinghai-Tibet Plateau. Fourteen DFR genomovars of Y. pestis were found and exhibited a significant region-specific distribution. Additionally, the increased genetic diversity of plague hosts is positively associated with human plague outbreaks. This insight gained can improve our understanding of biodiversity for pathogen spillover and provide municipally directed targets for One Health surveillance development, which will be an informative next step toward increased monitoring of M. himalayana dynamics.

Background: The major histocompatibility complex (MHC) plays a key role in the adaptive immune response to pathogens due to its extraordinary polymorphism. However, the spatial patterns of MHC variation in the striped hamster remain unclear, particularly regarding the relative contribution of the balancing selection in shaping MHC spatial variation and diversity compared to neutral forces. Methods: In this study, we investigated the immunogenic variation of the striped hamster in four wild populations in Inner Mongolia which experience a heterogeneous parasitic burden. Our goal was to identify local adaptation by comparing the genetic structure at the MHC with that at seven microsatellite loci, taking into account neutral processes. Results: We observed significant variation in parasite pressure among sites, with parasite burden showing a correlation with temperature and precipitation. Molecular analysis revealed a similar co-structure between MHC and microsatellite loci. We observed lower genetic differentiation at MHC loci compared to microsatellite loci, and no correlation was found between the two. Conclusions: Overall, these results suggest a complex interplay between neutral evolutionary forces and balancing selection in shaping the spatial patterns of MHC variation. Local adaptation was not detected on a small scale but may be applicable on a larger scale.

Background: The major histocompatibility complex (MHC) plays a key role in the adaptive immune response to pathogens due to its extraordinary polymorphism. However, the spatial patterns of MHC variation in the striped hamster remain unclear, particularly regarding the relative contribution of balancing selection in shaping MHC population and diversity compared to neutral forces. Methods: In this study, we investigated the immunogenic variation of the striped hamster in four wild populations in Inner Mongolia, which experience heterogeneous parasitic stress. Our goal was to identify local adaptation by comparing the genetic structure at MHC with that at seven microsatellite loci, taking into account neutral processes. Results: We observed significant variation in parasite pressure among sites, with parasite burden showing a correlation with temperature and precipitation. Molecular analysis revealed a similar co-structure between MHC and microsatellite loci. We observed lower genetic differentiation at MHC loci compared to microsatellite loci, and no correlation was found between the two. Conclusions: Overall, these results suggest a complex interplay between neutral evolutionary forces and balancing selection in shaping the spatial patterns of MHC variation. Local adaptation was not detected at a small scale but may be applicable at a larger scale.

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease that has threatened Chinese residents for nearly a century. Although comprehensive prevent and control measures were taken, the HFRS epidemic in China presents a rebounding trend in some areas. Urbanization is considered as an important influencing factor for the HFRS epidemic in recent years; however, the relevant research has not been systematically summarized. This review aims to summarize urbanization-related environmental factors and the HFRS epidemic in China and provide an overview of research perspectives. The literature review was conducted following the PRISMA protocol. Journal articles on the HFRS epidemic in both English and Chinese published before 30 June 2022 were identified from PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI). Inclusion criteria were defined as studies providing information on urbanization-related environmental factors and the HFRS epidemic. A total of 38 studies were included in the review. Changes brought by urbanization on population, economic development, land use, and vaccination program were found to be significantly correlated with the HFRS epidemic. By changing the ecological niche of humans—affecting the rodent population, its virus-carrying rate, and the contact opportunity and susceptibility of populations—urbanization poses a biphasic effect on the HFRS epidemic. Future studies require systematic research framework, comprehensive data sources, and effective methods and models.