The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

Role of postoperative chemoradiotherapy in head and neck cancer without positive margins or extracapsular extension: a propensity score-matching analysis.

BACKGROUND: The aim of this work was to determine whether patients with intermediate-risk head and neck squamous cell carcinoma (HNSCC) can benefit from postoperative chemoradiotherapy (POCRT). METHODS: Patients without extracapsular extension (ECE) or positive margins (PMs) who received POCRT or postoperative radiotherapy (PORT) at our center were retrospectively (December 2009 to October 2018) included for analysis, in particular, using a propensity score-matching method. RESULTS: After matching, 264 patients were enrolled, including 142 (41.2%) patients with pT3-4, 136 (38.3%) patients with pN2-3, 68 (21.1%) patients with perineural invasion, and 45 (12.8%) patients with lymphatic/vascular space invasion. With a median follow-up of 52 months, 3-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) rates were 72.4%, 79.3%, 83.5% and 62.5%, respectively. pN2-3 was an independent risk factor for OS (p < 0.001), DFS (p < 0.001), LRFS (p < 0.001) and DMFS (p = 0.002), while pT3-4 was a poor prognostic factor for DMFS (p = 0.005). Overall, patients receiving POCRT had no significant differences from those receiving PORT in OS (p = 0.062), DFS (p = 0.288), LRFS (p = 0.076) or DMFS (p = 0.692). But notably, patients with pN2-3 achieved better outcomes from POCRT than PORT in 3-year OS (p = 0.050, 63.9% vs. 47.9%) and LRFS (p = 0.019, 74.6% vs. 54.9%). And patients with pT3-4 also had higher 3-year LRFS (p = 0.014, 88.5% vs. 69.1%) if receiving POCRT. CONCLUSIONS: Among all intermediate-risk pathological features, pN2-3 and pT3-4 were independent unfavorable prognostic factors for patients with HNSCC without PMs or ECE. POCRT can improve the survival outcomes of patients with pN2-3 or pT3-4.

Modulation of Host Antiviral Innate Immunity by African Swine Fever Virus: A Review.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious and fatal disease found in swine. However, the viral proteins and mechanisms responsible for immune evasion are poorly understood, which has severely hindered the development of vaccines. This review mainly focuses on studies involving the innate antiviral immune response of the host and summarizes the latest studies on ASFV genes involved in interferon (IFN) signaling and inflammatory responses. We analyzed the effects of candidate viral proteins on ASFV infection, replication and pathogenicity and identified potential molecular targets for novel ASFV vaccines. These efforts will contribute to the construction of novel vaccines and wonder therapeutics for ASF.

Matrix-Directed Mineralization for Bulk Structural Materials.

Mineral-based bulk structural materials (MBSMs) are known for their long history and extensive range of usage. The inherent brittleness of minerals poses a major problem to the performance of MBSMs. To overcome this problem, design principles have been extracted from natural biominerals, in which the extraordinary mechanical performance is achieved via the hierarchical organization of minerals and organics. Nevertheless, precise and efficient fabrication of MBSMs with bioinspired hierarchical structures under mild conditions has long been a big challenge. This Perspective provides a panoramic view of an emerging fabrication strategy, matrix-directed mineralization, which imitates the in vivo growth of some biominerals. The advantages of the strategy are revealed by comparatively analyzing the conventional fabrication techniques of artificial hierarchically structured MBSMs and the biomineral growth processes. By introducing recent advances, we demonstrate that this strategy can be used to fabricate artificial MBSMs with hierarchical structures. Particular attention is paid to the mass transport and the precursors that are involved in the mineralization process. We hope this Perspective can provide some inspiring viewpoints on the importance of biomimetic mineralization in material fabrication and thereby spur the biomimetic fabrication of high-performance MBSMs.

Prognostic value of the neutrophil-to-lymphocyte ratio for hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis.

AIM: To investigate whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict the prognosis of hepatocellular carcinoma (HCC) patients with portal/hepatic vein tumor thrombosis (PVTT/HVTT) after hepatectomy. METHODS: The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed. RESULTS: Overall survival (OS) and disease-free survival (DFS) were determined in the patients with a high (> 2.9) and low (≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group (OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS (P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni- and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score (r = 0.276, P = 0.015) and the maximum diameter of the tumor (r = 0.435, P < 0.001). Additionally, the NLR could enhance the prognostic predictive power of the CLIP score for DFS in these patients. CONCLUSION: The preoperative NLR is a prognostic predictor after hepatectomy for HCC patients with PVTT/HVTT. NLR > 2.9 indicates poorer OS and DFS.

Epidemiologic characteristics of oral cancer: single-center analysis of 4097 patients from the Sun Yat-sen University Cancer Center.

BACKGROUND: Oral cancer is a common type of head and neck cancers. Knowing its epidemiologic characteristics is crucial to preventing, diagnosing, and treating this cancer. This study aimed to explore the epidemiologic characteristics of oral cancer in South China. METHODS: We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013. We compared the age of onset, sex ratio, pathologic type, and primary tumor location among three subcultural areas (Guangfu, Hakka, and Chaoshan) and between an economically developed region and a less-developed one in Guangdong. RESULTS: Overall, oral cancer had a male-to-female ratio of approximately 2:1, and this ratio decreased over time. Oral cancer occurred mostly in patients of 45-64 years old (54.5%), and the percentage of older patients gradually increased over time. The most common tumor location was the tongue. Squamous cell carcinoma was the predominant pathologic type. The percentage of blood type O in oral cancer patients was lower than that in the healthy population. The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas, whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan. The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region. CONCLUSION: The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.

[Laryngeal reconstruction by complex hyoid bone flap after frontal partial laryngectomy].

OBJECTIVE: The aim of this study was to describe a new technique of combined hyoid bone and thyrohyoid membrane flap in laryngeal reconstruction after tumor resection, and to evaluate outcome. METHODS: Six patients requiring an frontal partial laryngectomy for cancer were enrolled between September 2008 and August 2012. RESULTS: Nasogastric feeding was initiated within 24 hours. The mean times to swallow batter, ability to drink water and removal of the nasogastric tube were 2.6, 5.5 and 6.3 days. All patients had good respiratory function. There were no deaths, and no reports of postoperative dyspnea or dysphagia. The vocal quality was satisfactory, slightly deeper and raspy, and the volume was weak when calling. The final follow-up assessment was in August 2012, and the overall mean follow-up period was 29.5months, range 14 to 47 months. Case two subsequently underwent total laryngectomy for recurrence in the paraglottic space, but there was no evidence of further tumor recurrence at the final assessment. CONCLUSIONS: The combined muscle-pedicle hyoid bone and thyrohyoid membrane flap is a reliable graft for one-stage repair of laryngotracheal defects, providing effective repair of the mucosa and cartilage support. Vocal quality, swallowing function and ventilation after the procedure were favorable.