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Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen which causes significant economic losses in the global swine industry. Multiple vaccines have been developed to prevent PRRSV infection. However, they provide limited protection. Moreover, no effective therapeutic drugs are yet available. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV infection and transmission. Here we report that Toosendanin (TSN), a tetracyclic triterpene found in the bark or fruits of Melia toosendan Sieb. et Zucc., strongly suppressed type 2 PRRSV replication in vitro in Marc-145 cells and ex vivo in primary porcine alveolar macrophages (PAMs) at sub-micromolar concentrations. The results of transcriptomics revealed that TSN up-regulated the expression of IFI16 in Marc-145 cells. Furthermore, we found that IFI16 silencing enhanced the replication of PRRSV in Marc-145 cells and that the anti-PRRSV activity of TSN was dampened by IFI16 silencing, suggesting that the inhibition of TSN against PRRSV replication is IFI16-dependent. In addition, we showed that TSN activated caspase-1 and induced maturation of IL-1beta in an IFI16-dependent pathway. To verify the role of IL-1beta in PRRSV infection, we analyzed the effect of exogenous rmIL-1beta on PRRSV replication, and the results showed that exogenous IL-1beta significantly inhibited PRRSV replication in Marc-145 cells and PAMs in a dose-dependent manner. Altogether, our findings indicate that TSN significantly inhibits PRRSV replication at very low concentrations (EC50: 0.16-0.20 muM) and may provide opportunities for developing novel anti-PRRSV agents.Copyright © 2022, The Author(s).

INTRODUCTION: This study aimed to develop an automatic pipeline for analyzing mandibular shape asymmetry in 3-dimensions. METHODS: Forty patients with skeletal Class I pattern and 80 patients with skeletal Class III pattern were used. The mandible was automatically segmented from the cone-beam computed tomography images using a U-net deep learning network. A total of 17,415 uniformly sampled quasi-landmarks were automatically identified on the mandibular surface via a template mapping technique. After alignment with the robust Procrustes superimposition, the pointwise surface-to-surface distance between original and reflected mandibles was visualized in a color-coded map, indicating the location of asymmetry. The degree of overall mandibular asymmetry and the asymmetry of subskeletal units were scored using the root-mean-squared-error between the left and right sides. These asymmetry parameters were compared between the skeletal Class I and skeletal Class III groups. RESULTS: The mandible shape was significantly more asymmetrical in patients with skeletal Class III pattern with positional asymmetry. The condyles were identified as the most asymmetric region in all groups, followed by the coronoid process and the ramus. CONCLUSIONS: This automated approach to quantify mandibular shape asymmetry will facilitate high-throughput image processing for big data analysis. The spatially-dense landmarks allow for evaluating mandibular asymmetry over the entire surface, which overcomes the information loss inherent in conventional linear distance or angular measurements. Precise quantification of the asymmetry can provide important information for individualized diagnosis and treatment planning in orthodontics and orthognathic surgery.

The failure of transpassive films on transition metal alloys was investigated. The results show that the failure of the transpassive film on 3D printing nickel-based superalloy in flowing NaNO3 solution is dominated by self-induced cracking of the film on niobium-segregated phases and the erosion-induced degradation on the film assisted by cation vacancy condensation at the metal/barrier layer interface. Secondary passivation induces the formation of a transpassive film, the nature of which has been debated for decades. The findings are consistent with a bi-layer structure comprising a point-defective barrier layer that grows into the substrate alloy and a precipitated outer layer.

Supply restoration from outages is essential for improving the reliability of active distribution networks (ADNs) after fault isolation. Soft open point (SOP) can adjust the power flow among feeders and provide voltage support for power outage areas. Considering the sequential coordination of switching operation and SOP control mode selection, a multi-stage supply restoration method with SOPs is proposed for ADNs. First, the sequential energization is formulated, in which the impact of SOP control mode on restoration sequence is analyzed. By providing voltage support, the coordination of SOPs will rapidly energize the outage area and improve the voltage profile. Then, a multi-stage restoration model with SOPs is proposed, in which reconfiguration of switches and control mode selection of SOPs are coordinated in sequence to maximize the load recovery level of ADNs. Through the switching action-time mapping, secure operation is ensured during the entire supply restoration process. Finally, the effectiveness of the proposed method is validated on a modified IEEE 33-node distribution system and practical distribution networks with four-terminal SOP. Results show that the proposed method can fully exploit the potential benefits of SOPs and effectively enhance the load recovery level of ADNs.