Lung cancer is the world's leading cause of cancer‐related morbidity and mortality despite advances in surgery, chemotherapy and immunotherapy; thus, there is an urgent need to find new molecules to develop novel treatment strategies. Although ncRNAs were found to account for 98% transcripts, the number of lncRNAs with distinct function in lung cancer is extremely limited. We previously demonstrated that Plasmodium infection inhibits tumour growth and metastasis, but the exact mechanisms involved have not been fully understood. In this study, we carried out RNA sequencing (RNA‐Seq) of tumour tissues isolated from LLC tumour‐bearing mice treated with either Plasmodium yoelli (Py)‐infected red blood cells or uninfected red blood cells. We found that F630028O10Rik (abbreviated as F63) is a novel lncRNA that was significantly up‐regulated in tumours isolated from mice treated with Py‐infected red blood cells compared to the control. By using gene silencing technique, F63 was found to inhibit both tumour Vascular Endothelial Growth Factor A (VEGFA) secretion and endothelial cells clone formation, migration, invasion and tube formation. Injection of cholesterol‐modified siRNA‐F63 into mice tumour tissues produced a significant increase in tumour volume, blood vessel formation and angiogenesis 17 days after injection. We further showed that inhibiting miR‐223‐3p results in the down‐regulation of VEGFA and VEGFR2 which are vital molecules for angiogenesis. These results reveal that F63 inhibit tumour growth and progression by modulating tumour angiogenesis suggesting F63 can be a novel lncRNA with great potential as a candidate molecule for gene therapy in lung cancer.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), which has been regarded as a persistent challenge for the pig industry in many countries. PRRSV is internalized into host cells by the interaction between PRRSV proteins and cellular receptors. When the virus invades the cells, the host antiviral immune system is quickly activated to suppress the replication of the viruses. To retain fitness and host adaptation, various viruses have evolved multiple elegant strategies to manipulate the host machine and circumvent against the host antiviral responses. Therefore, identification of virus–host interactions is critical for understanding the host defense against viral infections and the pathogenesis of the viral infectious diseases. Most viruses, including PRRSV, interact with host proteins during infection. On the one hand, such interaction promotes the virus from escaping the host immune system to complete its replication. On the other hand, the interactions regulate the host cell immune response to inhibit viral infections. As common antiviral drugs become increasingly inefficient under the pressure of viral selectivity, therapeutic agents targeting the intrinsic immune factors of the host protein are more promising because the host protein has a lower probability of mutation under drug-mediated selective pressure. This review elaborates on the virus–host interactions during PRRSV infection to summarize the pathogenic mechanisms of PRRSV, and we hope this can provide insights for designing effective vaccines or drugs to prevent and control the spread of PRRS.

Pyroptosis, a distinctive form of programmed cell death (PCD) characterized by its inflammatory nature, is triggered by the activation of pore-forming proteins known as gasdermins (GSDMs). This process is marked by progressive expansion of a pore within the cell, ultimately leading to cellular membrane disruption and the substantial release of intracellular contents. Pyroptosis plays a pivotal role in the eradication of intracellular pathogen replication niches and in the modulation of the immune system through the release of danger signals. Emerging evidence suggests that viruses have developed sophisticated strategies to evade immune surveillance and establish persistent infections by manipulating host pyroptotic pathway This review presents recent advances on the mechanisms by which two major pathogens (virus and bacteria) activate or inhibit the pyroptosis process through their effector proteins, thereby facilitating their dissemination and blocking host immunity. These insights provide new perspectives on the regulatory mechanisms of interactions between hosts and pathogens in the pyroptosis process.

Given the rise of parasite resistance to all currently used antimalarial drugs, the identification of novel chemotypes with unique mechanisms of action is of paramount importance. Since Plasmodium expresses a number of aspartic proteases necessary for its survival, we have mined antimalarial datasets for drug-like aspartic protease inhibitors. This effort led to the identification of spiropiperidine hydantoins, bearing similarity to known inhibitors of the human aspartic protease β-secretase (BACE), as new leads for antimalarial drug discovery. Spiropiperidine hydantoins have a dynamic structure-activity relationship profile with positions identified as being tolerant of a variety of substitution patterns as well as a key piperidine N-benzyl phenol pharmacophore. Lead compounds 4e (CWHM-123) and 12k (CWHM-505) are potent antimalarials with IC50 values against Plasmodium falciparum 3D7 of 0.310 μM and 0.099 μM, respectively, and the former features equivalent potency on the chloroquine-resistant Dd2 strain. Remarkably, these compounds do not inhibit human aspartic proteases BACE, cathepsins D and E, or Plasmodium plasmepsins II and IV despite their similarity to known BACE inhibitors. Although the current leads suffer from poor metabolic stability, they do fit into a drug-like chemical property space and provide a new class of potent antimalarial agents for further study.

Orthobunyavirus refers to the virus members within the Genus Orthobunyavirus, which is the largest virus genus in the Family Peribunyaviridae and even Class Bunyaviricetes. To date, over 130 species of Orthobunyaviruses have been identified worldwide. Orthobunyaviruses mainly infect arthropods, while some species are capable of being transmitted to mammals, including humans, via intermediate vectors. As emerging and re-emerging pathogens, orthobunyavirus poses a significant threat to both human and veterinary public health worldwide. Currently, there are no commercial vaccines against orthobunyavirus. The structure of orthobunyavirus is relatively simple, consisting of a typical tri-segmented negative-sense RNA genome that encodes four structural proteins (L, Gn, Gc, and N) and two non-structural proteins (NSm and NSs). The highly glycosylated Gc protein, which has a complex conformation and forms polymers embedded in the viral envelope, plays a critical role in inducing neutralizing antibodies throughout the orthobunyavirus infection cycle from entry to egress. This review provides a comprehensive summary of the virus-encoded Gc protein and its role in the virus life cycle from viral entry to egress, offering researchers with valuable integrated information for further investigations.

The avian infectious bronchitis virus (IBV) poses a significant economic threat to the global poultry industry. Although in recent years, the GVI-1 lineage of IBV has proliferated throughout China, there is still a lack of comprehensive studies regarding the pathogenicity of this lineage, particularly with respect to infections of the digestive tract and the antigenic characteristics of the S1 gene. In this study, we investigated the effects of infecting 14-day-old chicks with the HX strain of the GVI-1 lineage over a 14-d period postinfection. Assessment of the pathogenicity of the HX strain included clinical observations; monitoring of body weight, organ viral load, viral shedding, and gross anatomy; histopathological analysis, and bioinformatics-based antigenic characterization of the S1 protein. The findings revealed that compared with previously reported GVI-1 lineage strains, the HX strain is characterized by greater virulence, with infection leading to approximately 26% mortality and extensive severe organ damage, including that of the proventriculus and kidneys. Moreover, at 14 d postinfection, 80% of oral swabs and 100% of cloacal swabs from chickens infected with the HX strain tested positive, indicating a prolonged period of viral shedding relative to that previously reported for GVI-1 lineage strains. Bioinformatic analysis of B-cell epitopes on the S1 protein revealed 7 potential antigenic epitopes. Collectively, our findings in this study provide clear evidence to indicate that compared previously reported GVI-1 lineage strains, chicks infected with the IBV GVI-1 lineage strain HX are characterized by heightened rates of mortality, more pronounced organ damage, and an extended period of viral shedding. This comprehensive characterization highlights the pathogenic potential of the GVI-1 lineage and its capacity to induce severe kidney and proventriculus damage, thereby emphasizing the imperative of early initiated preventive measures. Furthermore, on the basis of our analysis of the antigenic properties of the S1 protein, we have identified 7 potential linear B-cell epitopes, which will provide valuable insights for the development of epitope-based vaccines.