African swine fever (ASF) is a highly lethal contagious disease of swine caused by African swine fever virus (ASFV). At present, it is listed as a notifiable disease reported to the World Organization for Animal Health (OIE) and a class one animal disease ruled by Chinese government. ASF has brought significant economic losses to the pig industry since its outbreak in China in August 2018. In this review, we recapitulated the epidemic situation of ASF in China as of July 2020 and analyzed the influencing factors during its transmission. Since the situation facing the prevention, control, and eradication of ASF in China is not optimistic, safe and effective vaccines are urgently needed. In light of the continuous development of ASF vaccines in the world, the current scenarios and evolving trends of ASF vaccines are emphatically analyzed in the latter part of the review. The latest research outcomes showed that attempts on ASF gene-deleted vaccines and virus-vectored vaccines have proven to provide complete homologous protection with promising efficacy. Moreover, gaps and future research directions of ASF vaccine are also discussed.
Background As one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown. Methods BALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated. Results Hypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-β1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-β1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-β1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice. Conclusion Our findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.
Agents that target angiogenesis have shown limited efficacy for human triple-negative breast cancer (TNBC) in clinical trials. Along with endothelium-dependent vessels, there is also vasculogenic mimicry (VM) in the microcirculation of malignant tumors. The role of VM is not completely understood regarding anti-angiogenic treatment. In this study, human TNBC MDA-MB-231 and Hs578T and non-TNBC MCF-7 and BT474 tumor-bearing mice were treated with sunitinib, an anti-angiogenic drug, using a clinically relevant schedule. The drug was administered for one week and then discontinued. Tumor growth and invasion were observed, and the microcirculation patterns were detected with PAS/endomucin staining. Moreover, hypoxia and VM-associated proteins were evaluated with Hypoxyprobe kits and immunohistochemistry, respectively. Sunitinib significantly inhibited tumor growth in the TNBC and non-TNBC tumors. However, MDA-MB-231 and Hs578T tumors regrew and were more aggressive when the treatment was stopped. The discontinuation had no significant effect on the behavior of the non-TNBC MCF-7 and BT474 tumors. The growth of endothelium-dependent vessels in the TNBC MDA-MB-231 and Hs578T tumors were blocked by sunitinib, during which the number of VM channels significantly increased and resulted in a rebound of endothelium-dependent vessels after sunitinib discontinuation. Moreover, the VM-associated proteins VE-cadherin and Twist1 upregulated in the sunitinib-treated MDA-MB-231 and Hs578T tumors. Furthermore, the clinical significance of this upregulation was validated in 174 human breast cancers. The results from human breast cancer specimens indicated that there were more VM-positive TNBC cases than those in non-TNBC cases. HIF-1a, MMP2, VE-cadherin, and Twist1 were also expressed in a higher level in human TNBC compared with non-TNBC. In aconclusion, sunitinib promoted TNBC invasion by VM. The VM status could be helpful to predict the efficacy of anti-angiogenic therapy in patients with TNBC.
Aim: The aim of this study was to evaluate the prognostic significance of the preoperative systemic immune-inflammation index (SII) and to establish a nomogram for prediction of survival of tongue squamous cell carcinoma (TSCC) patients who underwent primary surgery and cervical dissection.Methods: 120 patients diagnosed with TSCC who underwent primary tumor and neck dissection without preoperative treatment were included to develop the nomogram. This model was externally validated in an independent data cohort of 50 TSCC patients. X-tile software was used to identify the optimal cut-off value. Prognostic factors were identified by Univariate and multivariate analyses. A nomogram based on the multivariate analysis results was built to predict the survival rate and calibration curves and concordance index (C-index) were used to determine predictive and discriminatory capacity.Results: The optimal cut-off value was 569×10 9 /L for SII. In the training cohort, a high preoperative SII (>569) was significantly related to tumor size, histological grade, depth of invasion, lymph node density (LND). A Kaplan-Meier survival analysis showed that patients with a lower SII had a significantly better 5-year overall survival (OS) and disease-free survival (DFS) than patients with high SII (80.8% vs. 43.5% and 72.7% vs. 36.2%, respectively, P<0.001). Univariate analyses of training cohort revealed that age, clinical stage, depth of invasion, LND, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and SII were significant prognostic factors for OS. Moreover, the receiver operating characteristics (ROC) curve showed that SII was superior to NLR and PLR for predicting clinical outcomes. However, multivariate analysis found that age, LND, and SII were independent risk factors for OS. The C-index of the nomograms based on independent prognostic factors was 0.716 for OS and 0.723 for DFS. The C-indexes for external validation of OS and DFS were 0.852 and 0.754, respectively. The calibration curves showed good agreement between predicted and actual observations of OS and DFS. Lu et al. SII Predict Survival of TSCCConclusion: SII can serve as a novel independent prognostic factor for OS and DFS of patients with TSCC. The prognostic nomogram based on SII is a reliable model for predicting survival of patients with TSCC after surgery.
Exploiting high-efficiency and low-cost bifunctional electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) has been actively encouraged because of their potential applications in the field of clean energy. In this paper, we reported a novel electrocatalyst based on an exfoliated two-dimensional (2D) MXene (TiCT ) loaded with bimetallic oxide alloy nanoparticles (NPs) of Pt and Pd (represented by PtOPdO NPs@TiCT ), which was synthesized via solution plasma (SP) modification. The prepared materials were then utilized as highly efficient bifunctional electrocatalysts toward the HER and OER in alkaline solution. At a high plasma input power (200 W), bimetallic oxide alloy nanoparticles of Pt and Pd or nanoclusters with different metallic valence states were deposited onto the TiCT nanosheets. Because of the synergism of the noble-metal NPs and the TiCT nanosheets, the electrocatalytic results revealed that the as-prepared PtOPdO NPs@TiCT nanosheets under the plasma input power of 200 W for 3 min only required a low overpotential to attain 10 mA cm for the HER (-26.5 mV) in 0.5 M HSO solution and OER (1.54 V) in 0.1 M KOH solution. Moreover, water electrolysis using this catalyst achieved a water splitting current density of 10 mA cm at a low cell voltage of 1.53 V in 1.0 M KOH solution. These results suggested that the hybridization of the extremely low usage of PtO /PdO NPs (1.07 μg cm) and TiCT nanosheets by SP will expand the applications of other clean energy reactions to achieve sustainable energy.
Accurate delineation of individual teeth and alveolar bones from dental cone-beam CT (CBCT) images is an essential step in digital dentistry for precision dental healthcare. In this paper, we present an AI system for efficient, precise, and fully automatic segmentation of real-patient CBCT images. Our AI system is evaluated on the largest dataset so far, i.e., using a dataset of 4,215 patients (with 4,938 CBCT scans) from 15 different centers. This fully automatic AI system achieves a segmentation accuracy comparable to experienced radiologists (e.g., 0.5% improvement in terms of average Dice similarity coefficient), while significant improvement in efficiency (i.e., 500 times faster). In addition, it consistently obtains accurate results on the challenging cases with variable dental abnormalities, with the average Dice scores of 91.5% and 93.0% for tooth and alveolar bone segmentation. These results demonstrate its potential as a powerful system to boost clinical workflows of digital dentistry.
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