No abstract

Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans.To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that microRNAs (miRNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes miRNAs for immune evasion. EBV encodes miRNAs targeting both viral and host genes involved in the immune response. The miRNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4 + and CD8 + T cell response of infected cells. These reports strongly indicate that EBV miRNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host miRNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated miRNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment. During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of miRNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants—alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 μg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a “spike protein-CD147-CyPA signaling axis”: Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

BackgroundAs an available new tool for spinal surgery, robotic technology holds great potential and has been demonstrated to have better clinical outcomes compared with traditional techniques. However, it has not been compared with other assisted tools for the treatment of lumbar degenerative disease. This article focused on studying such variances.Material/MethodsA total of 176 pedicle screws were inserted in 39 patients using a spine robot (group 1), 134 screws were implanted in 28 patients using navigational template (group 2), 234 screws were implanted in 51 patients by O-arm-based navigation (group 3), and 346 screws were implanted in 72 patients by fluoroscopy-guided assistance (group 4). The screw position was evaluated using postoperative scans according to Rampersaud A to D classification, and other secondary data were also collected.Results“Perfect” pedicle screw insertion (Grade A) was 90.34%, 91.79%, 84.19%, and 65.03% of groups 1–4, respectively. “Clinically acceptable” screw implantation (Grade A+B) was 94.32%, 95.52, 90.60%, and 78.03% in groups 1–4, respectively. Deviation sagittal (°) respectively was 3±9, 2±10, 4±7, and 10±8° in groups 1–4, respectively. Deviation transversal (°) screw insertion was 3±8, 3±7, 4±9, and 8±13° in groups 1–4, respectively. Statistical analysis showed group 1 had no significant difference in the accuracy of “Perfect and Clinical acceptable” as well as deviation sagittal or transversal, respectively, compared with groups 2 and 3 but not group 4.ConclusionsRobotic-assistance technology no clear advantage in terms of accuracy compared to the navigation template or O-arm systems for screw implantation, but it significantly reduced adverse events, fluoroscopy time per screw, postoperative stay, and blood loss.