Pentatrichomonas hominis is a flagellated protozoan that inhabits the large intestine of humans. Although several protozoans have been proposed to have a role in cancer progression, little is known about the epidemiology of P. hominis infection in cancer patients. To determine the prevalence of P. hominis in patients with digestive system malignancies, we collected 195 and 142 fecal samples from gastrointestinal cancer patients and residents without any complaints related to the digestive system, respectively. Each sample was detected for the presence of P. hominis by nested PCR amplifying the internal transcribed spacer (ITS) region and partial 18S rRNA gene. A significantly higher prevalence of P. hominis was found in cancer patients than that in the control population (41.54 vs 9.15%, χ2 = 42.84, df = 1, P < 0.001), resulting in a 6.75-fold risk of gastrointestinal cancers (OR: 6.75, 95% CI: 3.55–12.83, P < 0.001). The highest prevalence of P. hominis infection was detected in small intestine cancer patients (60%, OR: 14.88, 95% CI: 0.82–4.58, P = 0.009) followed by liver (57.14%, χ2 = 10.82, df = 1, P = 0.001) and stomach cancer patients (45.1%, χ2 = 31.95, df = 1, P < 0.001). In addition, phylogenetic analysis provided some evidence supporting that human P. hominis infection might derive from animal sources. To our knowledge, this study is the first report presenting the high association between P. hominis and gastrointestinal cancers. Nevertheless, whether there is any possible pathological role of P. hominis infection in cancer patients needs to be further elucidated.

In-wheel-motor-driven electric vehicles (IWM-EVs) provide more potential to enhance vehicle stability performance. However, traditional stability control relies on the current status fed back by sensors for stability judgment and control, only taking effect after the vehicle has already become unstable. In response to this issue, this paper proposes a pre-stability control strategy based on a hybrid dynamic state prediction method to predict dangerous driving conditions and intervene in vehicle stability control in advance. First, a driver-vehicle model is established to characterize the driver's driving intention and obtain the vehicle's ideal motion responses. Then, the methodology for implementing vehicle pre-stability control is introduced, which mainly includes sideslip angle estimation utilizing the extended Kalman filter, a hybrid dynamic state prediction approach based on vehicle model and data trends, and a vehicle pre-stability judgment method. Subsequently, a vehicle hierarchical controller is designed to achieve pre-stability control. The upper-level controller focuses on calculating the required additional yaw moment, and the lower-level controller aims to optimize torque distribution among the four wheels. Finally, the proposed pre-stability control strategy is validated by the hardware-in-the-loop test bench. The results show that the proposed control strategy can intervene in dangerous driving conditions in advance, and its mean errors of the yaw rate and sideslip angle are reduced by over 17.1% and 23.5%, respectively, compared with the traditional method, which significantly enhances vehicle stability and driving safety.

Neospora caninum is an intracellular parasite that causes significant economic losses in cattle industry. Understanding the host resistance mechanisms in the innate immune response to neosporosis could facilitate the exploration of approaches for controlling N. caninum infection. The NLR inflammasome is a multiprotein platform in the cell cytoplasm and plays critical roles in the host response against microbes. Neospora caninum-infected wild-type (WT) macrophages and Nlrp3 −/− macrophages, and inhibitory approaches were used to investigate inflammasome activation and its role in N. caninum infection. Inflammasome RT Profiler PCR Arrays were used to identify the primary genes involved in N. caninum infection. The expression of the sensor protein NLRP3, processing of caspase-1, secretion of IL-1β and cell death were detected. Neospora caninum replication in macrophages was also assessed. Many NLR molecules participated in the recognition of N. caninum, especially the sensor protein NLRP3, and further study revealed that the NLRP3 distribution became punctate in the cell cytoplasm, which facilitated inflammasome activation. Inflammasome activation-mediated caspase-1 processing and IL-1β cleavage in response to N. caninum infection were observed and were correlated with the time of infection and number of infecting parasites. LDH-related cell death was also observed, and this death was regarded as beneficial for the clearance of N. caninum. Treatment of N. caninum-infected macrophages with caspase-1, pan-caspase and NLRP3 inhibitors led to the impaired release of active IL-1β and a failure to restrict parasite replication. And Neospora caninum infected peritoneal macrophages from Nlrp3-deficient mice displayed greatly decreased release of active IL-1β and the failure of caspase-1 cleavage. The NLRP3 inflammasome can be activated in N. caninum-infected macrophages, and plays a protective role in the host response to control N. caninum.

Neospora caninum is an obligate intracellular parasite, which causes significant economic losses in the cattle industry. However, the immune mechanism of the parasite–host interaction is not yet fully understood. Extracellular vesicles (EVs) have emerged as a ubiquitous mechanism by which almost all cells, especially immune and tumor cells, participate in intercellular communications. Although studies have indicated that EVs secreted by Toxoplasma gondii or Trypanosoma brucei promote exchanges of biological molecules important for the host–parasite interplay, however, EVs and their biological activities in N. caninum is not clear. Here, we used multiple methods, including electron microscopy, nanoparticle tracking analysis, RT-PCR, immunofluorescence, western blot, proteomics, and cytokine analyses, to examine the properties of N. caninum EVs. We found that N. caninum produced EVs that are similar to mammalian exosomes, which generally range from 30 to 150 nm in diameter. It was shown that N. caninum EVs could remarkably increase the production of pro-inflammatory cytokines IL-12p40, TNF-α, IL-1β, IL-6, and IFN-γ by wild-type (WT) mouse bone marrow-derived macrophages (BMDMs) whereas the secretion of IL-12p40, TNF-α, and IFN-γ was very strongly downregulated in TLR2^−/− mouse BMDMs. The levels of IL-6 were not affected, but the secretion of IL-10 was upregulated. We found that the phosphorylation levels of P38, ERK, and JNK were significantly reduced in the TLR2^−/− cells compared with those in WT mouse BMDMs and that treatment with chemical inhibiters of P38, ERK, and JNK resulted in upregulation of IL-6, IL-12p40, and IL-10 production. Together, these results demonstrated that N. caninum EVs could be rapidly internalized to deliver proteins to the host cells and modulate the host cell immune responses through MAPK signaling pathway in a TLR2-dependent manner. Our study is the first to reveal potential roles for N. caninum EVs in host communication and immune response in parasite–host interactions.

Giardia infection is one of the most common causes of waterborne diarrhoeal disease in a wide array of mammalian hosts, including humans globally. Although numerous studies have indicated that adaptive immune responses are important for Giardia defense, however, whether the host innate immune system such as TLRs recognizes Giardia remains poorly understood. TLR2 plays a crucial role in pathogen recognition, innate immunity activation and the eventual pathogen elimination. In the present study, we investigated the role of TLR2 as a non-protective inflammatory response on controlling the severity of giardiasis. RT-PCR analysis suggested that TLR2 expression was increased in vitro. We demonstrated that G. lamblia induced cytokines expression by the activation of p38 and ERK pathways via TLR2. Interestingly, the expression of IL-12 p40, TNF-α, and IL-6, but not IFN-γ, was enhanced in TLR2-blocked and TLR2-/- mouse macrophages exposed to G. lamblia trophozoites compared with WT mouse macrophages. Further analysis demonstrated that G. lamblia trophozoites reduced cytokines secretion by activating AKT pathway in Wild Type (WT) mouse macrophages. Immunohistochemical staining in G. lamblia cysts infected TLR2-/- and WT mice showed that TLR2 was highly expressed in duodenum in infected WT mice. Also, infected TLR2-/- and AKT-blocked mice showed an increased production of IL-12 p40 and IFN-γ compared with infected WT mice at the early stage during infection. Interestingly, infected TLR2-/- and AKT-blocked mice displayed a decreased parasite burden，an increased weight gain rate and short parasite persistence. Histological morphometry showed shortened villus length, hyperplastic crypt and decreased ratio of villus height/crypt depth in infected WT mice compared with in infected TLR2-/- and AKT-blocked mice. Together, our results suggested that TLR2 deficiency lead to alleviation of giardiasis and reduction of parasite burden through the promotion of proinflammatory cytokines production. For the first time our results demonstrated that TLR2 played a negative role in host defense against Giardia. Keywords: Giardia, giardiasis, TLR2, TLR2-/-, AKT, cytokines.