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Four highly rearranged tetranorvibsane-type diterpenoids, vibsanoids A–D, with an unprecedented tricyclo[8.2.1.02,9]tridecane skeleton were isolated from Viburnum odoratissimum.

Objective. To explore the potential mechanism of Huanglian Jiedu Decoction (HJD) treatment and prevention of metastatic Cutaneous Melanoma (CM) occurrence and metastasis based on network pharmacological methods and immune infiltration analysis. Methods. The GEO database was used to obtain metastatic CM disease targets, the TCMSP database and the HERB database were used to obtain HJD action targets, core genes were screened by protein interaction network, and the potential mechanism of HJD in the treatment of metastatic CM was explored by enrichment analysis, prognostic analysis and immune infiltration analysis. Results. HJD treatment of metastatic CM involved 60 targets, enrichment analysis showed that HJD treatment of metastatic CM involved Chemokine signaling pathway, NF-kappa B signaling pathway, and Fluid shear stress and atherosclerosis, etc. Prognostic analysis revealed that HJD had a certain ability to improve the prognosis of metastatic CM patients. Immune infiltration analysis showed that HJD could inhibit the immune cell infiltration of metastatic CM patients by acting on related targets. Conclusions. Our study identified the potential mechanism of HJD in the treatment of metastatic CM through network pharmacology, and revealed the mechanism of HJD in the prevention of Skin Cutaneous Melanoma metastasis through immune infiltration analysis and prognostic analysis.

'Thai Gold' yellow pitahaya (family Cactaceae

'Purple Dream' eggplant (

Viroids are naked non-coding RNAs that can infect plants and cause severe disease. Apple scar skin viroid (ASSVd) is the causal agent of apple scar skin disease, which can infect apple trees and cause dappling and scar skin symptoms. In this study, we investigated the incidence of apple scar skin disease in apple-grafted small apple tree (Malus pumila ‘Saiwaihong’) in North China. Of 1322 tested trees, 90 exhibited obvious dapple symptoms in fruit skin (disease incidence of 6.8%). Dot-blot hybridization analysis proved that the peel from 25 diseased small apple tree were all positive for ASSVd, confirming that disease was associated with ASSVd infection. RT-PCR, cloning and sequencing were performed, and 12 complete sequences of ASSVd variants from Malus pumila ‘Saiwaihong’ were obtained. Sequence comparison showed that the 12 sequence variants shared 90.6–99.7% sequence similarity, phylogenetic analysis, performed based on the 12 ASSVd Malus pumila ‘Saiwaihong’ variants and other ASSVd variants reported from different hosts, did not show any clustering according to the respective host species. This is the first report of ASSVd infection in small apple tree (Malus pumila ‘Saiwaihong’).

Foot and mouth disease virus (FMDV), a member of family Picornaviridae, belongs to the genus Aphthovirus, which causes foot and mouth disease (FMD), a highly transmissible disease that affects cloven-hoof animals. In spite of the fact that efficient vaccines are available, effective antiviral molecules for FMD are needed to reduce viral infection during early stages of infection. In this study, merimepodib was found to efficiently inhibit FMDV replication in a dose-dependent manner. The 50% inhibitory concentration (IC50) of merimepodib antiviral activity against two distinct FMDV strains (O/MYA98/BY/2010 and A/GD/MM/CHA/2013) was estimated to be 7.859 and 2.876 μM, respectively, while the 50% cytotoxic concentration (CC50) of merimepodib was found to be 47.74 μM. Furthermore, treatment with 30 μg merimepodib efficiently prolonged the survival time of suckling mice infected with FMDV. Taken together, these results suggested that merimepodib has the potential to be a novel antiviral agent against FMDV.

Foot‐and‐mouth disease (FMD) is a highly contagious disease that affects cloven‐hoof animals including cattle, swine, sheep, goats, and lots of wild species. Effectively control measures are urged needed. Here, we showed that homoharringtonine treatment exhibited a strong inhibitory effect against two different strains of FMDVs (O/MYA98/BY/2010 and A/GD/MM/2013) in swine kidney (IBRS‐2) cells. Further experiments demonstrated that homoharringtonine did not affect virus attachment or entry. Using time‐of‐addition assays, we found that the antiviral activity of homoharringtonine occurred primarily during the early stage of infection. These results demonstrated that homoharringtonine might be an effective anti‐FMDV drug. Further studies are required to explore the antiviral activity of homoharringtonine against FMDV replication in vivo., Highlight This is the first study to demonstrate the antiviral activity of homoharringtonine against FMDV, including two different serotypes of FMDV in cell culture.Homoharringtonine did not suppress the attachment and entry of FMDV into the cell.The antiviral effect of homoharringtonine occurred in the early phases of FMDV replication.

Recently, a novel type I interferon alphaomega (IFN-αω), also known as IFN-μ, was identified. However, the biological activity of IFN-αω remain poorly understood. In this study, the porcine IFN-αω (PoIFN-αω) was expressed, purified, and its antiviral activities assessed by its ability to inhibit the cytopathic effect caused by FMDV on IBRS-2 cells. In addition, q-PCR was used to evaluate the expression of IFN-stimulated genes induced by PoIFN-αω. It was found that PoIFN-αω exerted effective antiviral activity against FMDV pre- and post-infection. Additionally, PoIFN-αω induced the transcription of IFN-stimulated genes, including Mx1, ISG15, OAS1, and PKR genes. Our study reported a new indication of PoIFN-αω as an effective anti-FMDV agent for the first time.

Background An increasing body of research has confirmed the effectiveness of Traditional Chinese Medicine (TCM) for the treatment of irritable bowel syndrome (IBS).Methods We explored the potential mechanism of Changping decoction (CPD) in the treatment of IBS through pathway analysis based on a network pharmacology approach. Public databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Gene Expression Omnibus, and STRING, were used to screen the active ingredients and targets of CPD. Enrichment analysis was performed using the R-3.6.0 software to expound the biological functions and related pathways of CPD targets. The Cytoscape software was used to construct a “disease-CPD-target” network and identify hub genes of CPD relevant for the treatment of IBS. Employing rat models, pathological observation and abdominal withdrawal reflex tests were used to verify the effectiveness of CPD in the treatment of IBS. Immunohistochemistry was used to confirm the relationship between the CPD treatment and hub genes.Results Network pharmacological analysis of CPD for the treatment of IBS identified 159 active ingredients. A total of 118 key targets were identified, including MAPK8, VEGFA, PTGS2, and others. A series of signaling pathways, such as MAPK, Kaposi sarcoma-associated herpesvirus infection, and IL-17 signaling pathway were found to play an important role in the therapeutic mechanism of CPD in the treatment of IBS. Pathological observation and abdominal withdrawal reflex tests confirmed that the symptoms of IBS in rats were relieved by CPD. Moreover, immunohistochemistry confirmed that CPD could inhibit the expression of inflammation-associated factors, such as VEGFA, MAPK8, and PTGS2.Conclusions Based on network pharmacology analysis, the present study provides insights into the potential mechanism of CPD in the treatment of IBS after successfully screening for associated key target genes and signaling pathways. These findings establish a theoretical basis for the development of CPD-derived therapeutics.

Background: Immunotherapy, as a very promising treatment, has the potential to change the therapeutic landscape for malignancies. However, due to the complexity of immunotherapy and the heterogeneity of Hepatocellular carcinoma (HCC), it is crucial to grasp the characteristics of the tumour immune microenvironment to improve effects of immunotherapy. Methods: The ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm was used to calculate the immune and stromal scores for quantitative analysis of immune and stromal cell infiltration in HCC. The weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were analysed to identify immune microenvironment-related genes. Findings: Immune and stromal scores calculated by ESTIMATE closely represented immune cell components in the tumour microenvironment. Patients with high immune scores had a higher 4-year survival rate. TP53, CTNNB1, and AXIN1 mutations significantly varied with immune scores. In immune score-related modules analysis, Kyoto encyclopaedia of genes and genomes (KEGG) pathways and gene ontology (GO) terms were closely related to immune processes, tumorigenesis, and metastasis. Twelve new immune microenvironment-related genes were identified and had significantly positive correlations with seven checkpoint genes. In prognostic analysis, eleven immune microenvironment-related genes exhibited high expression, nine of which were validated in the GSE62232 dataset and were significantly associated with a good prognosis (P

Foot-and-mouth disease (FMD) is one of the most devastating diseases affecting livestock. Since vaccines fail to provide protection until seven days post-vaccination, the application of anti-viral molecules is imperative for suppressing the spread of FMDV prior to development of an adaptive immune response. Interferons (IFNs) are effective for the host to fight FMDV infections; however, a novel type I IFNs, interferon delta (IFN-δ), has not been investigated for their antiviral effects against this virus. Thus, this study investigated FMDV infection, upon pre- and post-treatment with PoIFN-δ8. Real-time quantitative PCR was used to quantify the expression levels of IFN-stimulated genes (ISGs), including ISG15, OAS1, PKR, and Mx1. Results showed the PoIFN-δ8 lacking its signal sequence was efficiently expressed in Escherichia coli, and the purified recombinant PoIFN-δ8 exerted a significantly protective effect against two different serotypes of FMDV in IBRS-2 cells. In addition, PoIFN-δ8 induced the expression of IFN-stimulated genes. These findings highlight the significance of PoIFN-δ might serve as an antiviral agent for the prevention of FMDV in pigs and will stimulate the study of exploiting the potential biological functions of IFN-δ in the future.

The common fig (Ficus carica L.) was one of the earliest horticultural crops to be domesticated. A number of different viruses can infect fig trees including Fig mosaic virus (FMV) that has been detected in several commercial fig trees in Xinjiang, China. However, the distribution of FMV and other fig-infecting viruses in China remains unknown. In the present study, a sample from an ancient fig tree growing in Xinjiang was investigated by electron microscopy (EM) followed by PCR/RT-PCR, and FMV, Fig badnavirus 1 (FBV-1) and Fig leaf mottle-associated virus 1 (FLMaV-1) were detected. Fig leaf samples (252) from commercial orchards across China were subjected to PCR/RT-PCR, and FMV, FBV-1 and Fig fleck-associated virus (FFkaV) were relatively abundant (44.4, 48.4 and 44%, respectively), while FLMaV-1 and Fig mild mottle-associated virus (FMMaV) were much scarcer (5.6 and 0.4%, respectively), and FLMaV-2, Fig cryptic virus (FCV), and Fig latent virus (FLV) were not detected. The presence of disease-causing viruses in fig trees presents a significant challenge for fig producers in China. This study may help to promote actions aimed at controlling fig viruses, especially FMV.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4–7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.

Seven new diterpenoids (1–7), including five 7-membered ring vibsane-type diterpenoids, vibsanolide A-E (1–5) and a pair of epimers of 14,15,16,17-tetranorvibsane-type diterpenoids possessing bicyclo[4.2.1]nonane moiety, vibsanolide F-G (6–7), together with twelve known analogues (8–19) were isolated from the crude extracts of the leaves of Viburnum odoratissimum using Small Molecule Accurate Recognition Technology (SMART). These structures including absolute configurations were elucidated by means of comprehensive analyses of spectroscopic data, as well as comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. These compounds were evaluated for their cytotoxic activities against A549 and HepG2 cells by MTT assay. The results showed that compound 2 exhibited potent cytotoxic activity against A549 cells with IC50 value of 1.11 μM. Further staining experiments indicated that 2 could promote apoptosis induction, enhance reactive oxygen species (ROS) level and attenuate mitochondrial membrane potential (MMP) in A549 cells. Taken together, these findings provided new insights into understanding the cytotoxic activity of vibsane-type diterpenoids and it is meaningful to further investigate the application potential of V. odoratissimum.

[EN] Members of the family Avsunviroidae have a single-stranded circular RNA genome that adopts a rod-like or branched conformation and can form, in the strands of either polarity, hammerhead ribozymes involved in their replication in plastids through a symmetrical RNA-RNA rolling-circle mechanism. These viroids lack the central conserved region typical of members of the family Pospiviroidae. The family Avsunviroidae includes three genera, Avsunviroid, Pelamoviroid and Elaviroid, with a total of four species. This is a summary of the ICTV Report on the taxonomy of the family Avsunviroidae, which is available at /http:/www.ictv.global/report/avsunvirodae., Production of this summary, the online chapter and associated resources was funded by a grant from the Wellcome Trust (WT108418AIA).

A numerical simulation method is hereby adopted in this paper to calculate and analyze the thermal dispersion influence factors of three particle-shaped porous mediums of two-dimensional porous medium with different skeleton structures. Result shows that the thermal dispersion influence factors include fluid thermal properties, Darcy velocity, porosity and skeleton structure, etc. Under the same condition, the thermal dispersion coefficient of a circular particle model is maximum, and it increases with the rise of Pednumber; with the increase of the porosity or the reduction of Darcy velocity, the thermal dispersion coefficient reduces increasingly. When considering the thermal dispersion effect, the axial temperature variation of fluid is more applicable for numerical simulation, which proves that it shall consider the thermal dispersion during researches on porous medium models.

Since 1985, interferon (IFN)-ω, a type I IFN, has been identified in many animals, but not canines and mice. It has been demonstrated to have antiviral, anti-proliferation, and antitumor activities that are similar to those of IFN-α. To date, IFN-ω has been explored as a treatment option for some diseases or viral infections in humans and other animals. Studies have revealed that human IFN-ω displays antitumor activities in some models of human cancer cells and that it can be used to diagnose some diseases. While recombinant feline IFN-ω has been licensed in several countries for treating canine parvovirus, feline leukemia virus, and feline immunodeficiency virus infections, it also exhibits a certain efficacy when used to treat other viral infections or diseases. This review examines the known biological activity of IFN-ω and its clinical applications. We expect that the information provided in this review will stimulate further studies of IFN-ω as a therapeutic agent., Highlights • Few systemically review about interferon omega is online. • We provide a broad knowledge of the characteristics and biological functions of IFN-ω. • We examine the known information of IFN-ω which used as potential application in treating some diseases or virus.

Foot-and-mouth disease (FMD) is a significant zoonotic infectious disease. It has an important economic impact throughout the world. As well, it is a considerable threat to food security. At present, the molecular mechanism of FMDV infection is not clear to a large extent. Innate immune response is the first line of defense against infectious diseases. The systematic analysis of the host immune response to infection has an important role in understanding the pathogenesis of infection. However, there are few reports about effect of immune regulation on virus replication in the interaction of virus and host cellular. High-throughput RNA-seq technology as a powerful and efficient means for transcript analysis provides a new insight into FMDV study. In this study, RNA extracted from pig PBMCs infected with O subtype FMDV at 4 dpi. A total of 29942658 and 31452917 Illumina read pairs were obtained from the non-infected (NI) group and infected (I) group, respectively. The clean bases for all samples are 3.61G (NI group) and 3.79G (I group), respectively. The clean reads of the NI and I group that mapped to pig genome data were 47195073 (81.82%) and 46556714 (76.85%), respectively. Most of the clean reads were distributed in the exon region, followed by intron region and intergenic region. Differently expressed (DE) genes were analyzed using edgeR software. 451 genes were differentially expressed between the infected and the non-infected groups. According to the comparison analysis, more genes were down-regulated in the non-infected samples than in those infected with FMDV.66 out of 451 genes were down-regulated, 385 out of 451 genes were up-regulated following FMDV infection. For function classification and pathway analysis, among 17741 assembled unigenes, there are 349 genes which are different genes of GO notes. Moreover, 49 genes were down-regulated, 300 genes were up-regulated associate with GO term. 1621 were successfully annotated by GO assignments, belonging to one or more of the three categories: biological process, cellular component, and molecular function. According to KEGG analysis,the main pathway was represented including protein processing in endoplasmic reticulum, phagosome, cell cycle and cytokine-cytokine receptor interaction. Some key DE genes related to immune process and signaling pathways were analyzed and quantified by RT-PCR. This is the first systematical transcriptome analysis of pig PBMCs infected by FMDV. These findings will help us better understand the host Cell-FMDV interaction and its relationship to pathogenesis, as well as contribute to the prevention and control of FMDV.

The International Committee on Virus Taxonomy (ICTV) is the organization responsible for establishing the rules to classify viroids into species, genera, and families, and ultimately to endorse viroid taxonomy. The ICTV recently called for more stringent rules to create new virus and viroid species, which must be based on at least two independent criteria. This chapter discusses the resulting implications and presents an updated viroid classification scheme that takes into account the identification of new viroids by next-generation sequencing and bioinformatics tools, which ICTV may finally accept as new species.

OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF