Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus that is carried asymptomatically by wildebeest. Upon cross-species transmission to other ruminants, including domestic cattle, AlHV-1 induces malignant catarrhal fever (MCF), which is a fatal lymphoproliferative disease resulting from proliferation and uncontrolled activation of latently infected CD8 + T cells. Two laboratory strains of AlHV-1 are used commonly in research: C500, which is pathogenic, and WC11, which has been attenuated by long-term maintenance in cell culture. The published genome sequence of a WC11 seed stock from a German laboratory revealed the deletion of two major regions. The sequence of a WC11 seed stock used in our laboratory also bears these deletions and, in addition, the duplication of an internal sequence in the terminal region. The larger of the two deletions has resulted in the absence of gene A7 and a large portion of gene A8. These genes are positional orthologs of the Epstein-Barr virus genes encoding envelope glycoproteins gp42 and gp350, respectively, which are involved in viral propagation and switching of cell tropism. To investigate the degree to which the absence of A7 and A8 participates in WC11 attenuation, recombinant viruses lacking these individual functions were generated in C500. Using bovine nasal turbinate and embryonic lung cell lines, increased cell-free viral propagation and impaired syncytia formation were observed in the absence of A7, whereas cell-free viral spread was inhibited in the absence of A8. Therefore, A7 appears to be involved in cell-to-cell viral spread, and A8 in viral cellfree propagation. Finally, infection of rabbits with either mutant did not induce the signs of MCF or the expansion of infected CD8 + T cells. These results demonstrate that A7 and A8 are both essential for regulating viral spread and suggest that AlHV-1 requires both genes to efficiently spread in vivo and reach CD8 + T lymphocytes and induce MCF.

Human haemorrhoidal disease (HEM) is a common anorectal pathology. However, being one of the diseases that affect a wide range of people, the etiology of HEM, as well as its molecular mechanism, remains primarily unclear. In this study, we applied a two-sample bi-direction Mendelian randomization (MR) framework to estimate the causal effects of 4677 plasma proteins on HEM outcomes and investigated the mediating impacts of plasma proteins on HEM risk factors to uncover potential HEM treatment targets by integrating GWASs statistics of HEM and plasma protein levels. Following MR analysis, our study identified 13 probable causal proteins associated with HEM. Particularly, genetically predicted OLFM1 levels were linked to an increased risk of HEM. In addition, it was discovered that a genetically greater risk of myxoedema, diverticular disease, and ulcerative colitis was linked to an elevated risk of HEM (FDR<0.05). However, there was no evidence that dorsalgia, hernia, and ankylosing spondylitis were causally associated with HEM. Interestingly, a higher risk of myxoedema was associated with higher genetically predicted OLFM1 levels. Finally, mediation analysis suggested that the effect of myxoedema on HEM via OLFM1 might explain 32.8% of the mediation effect. Overall, this study identified some causal associations of circulating proteins and risk factors with HEM by integrating the largest-to-date plasma proteome and GWASs of HEM. The findings could provide further insight into understanding biological mechanisms for HEM.

Dupuytren's disease is a common localized fibrotic disorder that affects the palmar fascia. Recent research using single-cell RNA sequencing (scRNA-seq) has expanded our understanding of the main cellular and molecular processes in mesenchymal cells that drive Dupuytren's disease. However, the involvement of other cells in developing Dupuytren's disease is largely unresolved. Endothelial cells (ECs) play an important role in the pathophysiology of some fibrotic diseases, such as lung fibrosis, keloid, and systemic sclerosis, according to growing studies. In this study, scRNA-seq analysis from Dupuytren's disease, healthy dermis (DE), and nonpathogenic (Skoog's) fascia (SF) were performed to explore the major pathogenic ECs subpopulations associated with Dupuytren's disease. Our results showed that patients with Dupuytren's disease had a larger percentage of Endothelial cells with RGCC+ expression. We discovered the trajectory of differentiation from IL6+ ECs to RGCC+ ECs using RNA velocity and pseudotime analysis. Furthermore, utilizing integration analysis of DEG and hdWGCNA, the potential role of EC subpopulations involved in the disease was investigated. Finally, we identified potential endothelial cell transcription factors and investigated cell-cell communication among ECs. Overall, we discovered molecular features of ECs that relate to Dupuytren's disease at the single-cell level. These findings could contribute to our understanding of the pathogenesis of Dupuytren's disease.

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Dupuytren's disease is a common localized fibrotic disorder that affects the palmar fascia. Recent research using single-cell RNA sequencing (scRNA-seq) has expanded our understanding of the main cellular and molecular processes in mesenchymal cells that drive Dupuytren's disease. However, the involvement of other cells in developing Dupuytren's disease is largely unresolved. Endothelial cells (ECs) play an important role in the pathophysiology of some fibrotic diseases, such as lung fibrosis, keloid, and systemic sclerosis, according to growing studies. In this study, scRNA-seq analysis from Dupuytren's disease, healthy dermis (DE), and nonpathogenic (Skoog's) fascia (SF) were performed to explore the major pathogenic ECs subpopulations associated with Dupuytren's disease. Our results showed that patients with Dupuytren's disease had a larger percentage of Endothelial cells with RGCC+ expression. We discovered the trajectory of differentiation from IL6+ ECs to RGCC+ ECs using RNA velocity and pseudotime analysis. Furthermore, utilizing integration analysis of DEG and hdWGCNA, the potential role of EC subpopulations involved in the disease was investigated. Finally, we identified potential endothelial cell transcription factors and investigated cell-cell communication among ECs. Overall, we discovered molecular features of ECs that relate to Dupuytren's disease at the single-cell level. These findings could contribute to our understanding of the pathogenesis of Dupuytren's disease.