(SCMV) is one of the major pathogens of sugarcane. SCMV infection causes dynamic changes in plant cells, including decreased photosynthetic rate, respiration, and sugar metabolism. To understand the ...basics of pathogenicity mechanism, we performed transcriptome and proteomics analysis in two sugarcane genotypes (Badila: susceptible to SCMV and B-48: SCMV resistant). Using
L. genome as a reference, we identified the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) that participate in sugar metabolism, transport of their metabolites, and Carbohydrate Activating enZYmes (CAZymes). Sequencing data revealed 287 DEGs directly or indirectly involved in sugar metabolism, transport, and storage, while 323 DEGs are associated with CAZymes. Significant upregulation of glucose, sucrose, fructose, starch, and SWEET-related transcripts was observed in the Badila after infection of SCMV. B-48 showed resistance against SCMV with a limited number of sugar transcripts up-regulation at the post-infection stage. For CAZymes, only glycosyltransferase (GT)1 and glycosyl hydrolase (GH)17 were upregulated in B-48. Regulation of DEGs was analyzed at the proteomics level as well. Starch, fructose, glucose, GT1, and GH17 transcripts were expressed at the post-translational level. We verified our transcriptomic results with proteomics and qPCR data. Comprehensively, this study proved that Badila upregulated sugar metabolizing and transporting transcripts and proteins, which enhance virus multiplication and infectionl.
Huanglongbing (HLB) is a serious citrus disease that threatens the citrus industry. In previous studies, sulfonamide antibiotics and heat treatment suppressed 'Candidatus Liberibacter asiaticus' ...(Las), but did not completely eliminate the Las. Furthermore, there are few reports studying the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics. In this study, combinations of heat (45°C or 40°C) and sulfonamide treatment (sulfathiazole sodium-STZ, or sulfadimethoxine sodium-SDX) were applied to HLB-affected citrus. The bacterial microbiome of HLB-affected citrus following thermotherapy and/or chemotherapy was characterized by PhyloChipTMG3-based metagenomics. Our results showed that the combination of thermotherapy at 45°C and chemotherapy with STZ and SDX was more effective against HLB than thermotherapy alone, chemotherapy alone, or a combination of thermotherapy at 40°C and chemotherapy. The PhyloChipTMG3-based results indicated that 311 empirical Operational Taxonomic Units (eOTUs) were detected in 26 phyla. Cyanobacteria (18.01%) were dominant after thermo-chemotherapy. Thermotherapy at 45°C decreased eOTUs (64.43%) in leaf samples, compared with thermotherapy at 40°C (73.96%) or without thermotherapy (90.68%) and it also reduced bacterial family biodiversity. The eOTU in phylum Proteobacteria was reduced significantly and eOTU_28, representing "Candidatus Liberibacter," was not detected following thermotherapy at 45°C. Following antibiotic treatment with SDX and STZ, there was enhanced abundance of specific eOTUs belonging to the families Streptomycetaceae, Desulfobacteraceae, Chitinophagaceae, and Xanthomonadaceae, which may be implicated in increased resistance to plant pathogens. Our study further develops an integrated strategy for combating HLB, and also provides new insight into the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics.
Nitrogen availability might play an essential role in plant diseases by enhancing fungal cell growth and influencing the expression of genes required for successful pathogenesis. Nitrogen ...availability could modulate secondary metabolic pathways as evidenced by the significant differential expression of several core genes involved in mycotoxin biosynthesis and genes encoding polyketide synthase/nonribosomal peptide synthetases, cytochrome P450 and carbohydrate-active enzymes in
, grown on different nitrogen sources. A combined analysis was carried out on the transcript and metabolite profiles of regulatory metabolic processes and the virulence of
grown on various nitrogen sources. The nitrogen regulation of the gibberellin gene cluster included the metabolic flux and multiple steps of gibberellin synthesis. UHPLC-MS/MS-based metabolome analysis revealed the coordination of these related transcripts and the accumulation of gibberellin metabolites. This integrated analysis allowed us to uncover additional information for a more comprehensive understanding of biological events relevant to fungal secondary metabolic regulation in response to nitrogen availability.
Here we focus on the molecular characterization of clinically significant histological subtypes of early-stage lung adenocarcinoma (esLUAD), which is the most common histological subtype of lung ...cancer. Within lung adenocarcinoma, histology is heterogeneous and associated with tumor invasion and diverse clinical outcomes. We present a gene signature distinguishing invasive and non-invasive tumors among esLUAD. Using the gene signatures, we estimate an Invasiveness Score that is strongly associated with survival of esLUAD patients in multiple independent cohorts and with the invasiveness phenotype in lung cancer cell lines. Regulatory network analysis identifies aurora kinase as one of master regulators of the gene signature and the perturbation of aurora kinases in vitro and in a murine model of invasive lung adenocarcinoma reduces tumor invasion. Our study reveals aurora kinases as a therapeutic target for treatment of early-stage invasive lung adenocarcinoma.
Sugarcane mosaic virus
(SCMV), belonging to genus
Potyvirus
, family
Potyviridae
, is a severe pathogen of several agricultural important crops, mainly sugarcane. Due to complex nature of sugarcane, ...the effect of SCMV pathogenicity on sugarcane photosynthetic systems remains to be explored. In this study, we investigated the alterations occurring in the photosynthetic system in the sugarcane genotypes at the cytopathological, physiological and biological, transcriptome and proteome level. We generated the transcriptome assembly of two genotypes (susceptible Badila and resistant B-48) using
Saccharum spontaneum
L. as a reference genome. RNA-sequencing data revealed the significant upregulation of NAD(P)H, RubisCO, oxygen-evolving complex, chlorophyll
a
and
b
binding protein, Psb protein family, PSI reaction center subunit II, and IVgenes in B-48, as compared to its counterparts. Upregulated genes in B-48 are associated with various processes such as stability and assembly of photosystem, protection against photoinhibition and antiviral defense. The expression pattern of differentially abundant genes were further verified at the proteomics level. Overall, differentially expressed genes/proteins (DEGs/DEPs) showed the consistency of expression at both transcriptome and proteome level in B-48 genotype. Comprehensively, these data supported the efficiency of B-48 genotype under virus infection conditions and provided a better understanding of the expression pattern of photosynthesis-related genes in sugarcane.
Abstract Similar to the adenoma–carcinoma sequence of colorectal cancer, lung adenocarcinoma is thought to follow a linear multistep progression, in which a precursor lesion progresses to ...adenocarcinoma in situ , which is followed by invasive adenocarcinoma. However, lung adenocarcinoma can no longer be considered as a single type of tumor but rather a group of distinct subsets of tumors that arise from different molecular pathways. Consistent with this concept, recent findings revealed that this linear progression might not occur in all lung adenocarcinomas. First, according to the molecular classification based on expression profiling, lung cancer can be divided into at least two subsets; precancerous and in situ lesions share characteristics of molecular expression and clinical features with only one of the two subsets, suggesting that the linear progression is only applicable to the subset in the molecular classification. Second, when EGFR and KRAS were examined based on the progression steps, the mutation rate of KRAS was disproportionally distributed; however, according to the progression schema, gene alterations should be evenly accumulated along the entire progression. Third, by means of comparative genomic hybridization analysis, some adenocarcinoma in situ revealed gene alterations discontinuous to invasive adenocarcinoma. Finally, there were some clinical observations that support that some lesions escape from the progression. In this review, we hypothesize a novel scenario for the progression of lung adenocarcinoma, which does not support a linear progression schema.
Severe coronavirus disease 2019 causes multi-organ dysfunction with significant morbidity and mortality. Mounting evidence implicates maladaptive over-activation of innate immune pathways such as the ...complement cascade as well as endothelial dysfunction as significant contributors to disease progression. We review the complement pathways, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on these pathways, and promising therapeutic targets in clinical trials.
Limited resection has been increasingly used in older patients with stage IA lung cancer. However, the equivalency of limited resection versus lobectomy according to histology is unknown.
We ...identified patients older than 65 years with stage IA invasive adenocarcinoma or squamous cell carcinoma ≤ 2 cm who were treated with limited resection (wedge or segmentectomy) or lobectomy in the Surveillance, Epidemiology, and End Results-Medicare database. We estimated propensity scores that predicted the use of limited resection and compared survival of patients treated with limited resection versus lobectomy. Treatments were considered equivalent if the upper 95th percentile of the hazard ratio (HR) for limited resection was ≤ 1.25.
Overall, 27% of 2,008 patients with adenocarcinoma and 32% of 1,139 patients with squamous cell carcinoma underwent limited resection. Survival analyses, adjusted for propensity score by using inverse probability weighting, showed that limited resection was not equivalent to lobectomy in patients with adenocarcinoma (HR, 1.21; upper 95% CI,1.34) or squamous cell carcinoma (HR, 1.21; upper 95% CI, 1.39). Although patients with adenocarcinomas treated with segmentectomy had equivalent survival rates to those treated with lobectomy (HR, 0.97; upper 95% CI, 1.07), outcomes of those treated with wedge resection (HR, 1.29; upper 95% CI, 1.42) did not. Among patients with squamous cell carcinoma, neither wedge resection (HR, 1.34; upper 95% CI, 1.53) nor segmentectomy (HR, 1.19; upper 95% CI, 1.36) were equivalent to lobectomy.
We found generally that limited resection is not equivalent to lobectomy in older patients with invasive non-small-cell lung cancer ≤ 2 cm in size, although segmentectomy may be equivalent in patients with adenocarcinoma.
SEE PDF TECs could promote cancer progression by supporting tumor metabolism1 or secreting paracrine factors.2 Recently, by single-cell RNA sequencing (scRNA-seq), we could gain a landscape view of ...the dynamic gene network in the TECs.3 For example, in a metastatic melanoma study, Tirosh et al. identified that the TECs in the drug-resistant tumors harbored heterogeneous genetic signal compared to the normal ECs gene expression.4 The scRNA-seq analysis aims to discover the unique biomarker or signaling ligands/receptors on the cell population of interest. ...one scRNA-seq profiling of mouse lung endothelial cells defined a specific lung endothelial cell population,5 marked by carbonic anhydrase 4 (CA4), whose expression depends on VEGFA expression AT1-positive cells.6 The Notch ligand Dll4 was abundantly expressed by endothelial cells, impacting smooth muscle cells (SMC) and fibroblasts by binding with their Notch1 or Notch3 receptors (Figure 2).7 The other endothelial-specific markers include Ephrins8 and Slit2,9 as well as TEC specific tip cell-specific marker CXCR4, PGF and LXN, etc.10 The VEGF and Notch signaling pathways in tumor ECs could be more active than in the normal tissue endothelial cells, responsible for the upregulation of angiogenesis.11 The downregulation of gene expression related to immune activation in tumor ECs indicates that tumor ECs would suppress the antitumor immune function. Wang et al. developed an apelin-based synNotch receptors binding system to detect the angiogenic signaling within tumor.16 Based on scRNA-seq, one subgroup of TEC, tip TECs, correlated with patient survival. ...Tip TECs can be considered a potential marker to evaluate the effectiveness of VEGF blockade therapies.10 Besides, a higher proportion of endothelial cells can be harvested in clinical core biopsy samples than in surgical resection samples.17 Due to the technical difficulties of obtaining TECs, one approach is to apply a set of transgenetic reporter mice to capture endothelial cells in mouse models. ...IgG4+CD49b+CD73+ B cells expressing pro-angiogenic cytokine could efficiently promote endothelial cell tubes' formation in the tumor microenvironment.28 Regarding translational therapy, historically, anti-angiogenesis therapy targets tumor vascular network growth, which mainly consists of two mechanisms: (a) angiogenesis, the formation of new blood vessels from existing vessels, and (b) vasculogenesis, the de novo formation of blood vessels from endothelial precursors.29 Many growth factors promote angiogenic output (e.g., FGF, VEGF, IL-8, and PDGF) and endogenous inhibitors also exist to block vessel growth (e.g., thrombospondin, tumstatin, canstatin, endostatin, angiostatin, and interferon-alpha/beta).30 However, the targeted inhibition of the VEGF signaling has not always resulted in favorable outcomes in cancer patients' treatment.31 Recently, the combination of anti-PD-L1 and anti-VEGF therapy showed significant benefit in patients with unresectable hepatocellular carcinoma.32 It is hinted that the anti-VEGF neutralizing antibody reversed the immunosuppressive function of TECs and promoted T-cell infiltration in the tumor.
Pokkah boeng disease (PBD), a sugarcane foliar disease, is caused by various
spp. within the
species complex (FFSC). In the current study, we investigated the diversity of
spp. associated with PBD in ...China. In total, 320 leaf samples displaying PBD symptoms were collected over 10 consecutive years (2012 to 2021), during winter and summer, from six various sugarcane-growing regions (Guangxi, Yunnan, Guangdong, Zhejiang, Hainan, and Fujian) in China. Phylogenetic analysis of
spp. was reconstructed using translation elongation factor 1-α, and DNA-directed RNA polymerase II largest subunit and second-largest subunit multigene sequences. Evolutionary studies of these regions categorized the isolates into four FFSC species (
,
,
, and
). The identified isolates, which developed irregular necrotic patches and rotting symptoms on the sugarcane plant after approximately 30 days were tested for their pathogenicity. Symptoms that appeared during pathogenicity testing were consistent with those observed under field conditions. Each strain of the pathogenic
spp. belonged to different vegetative compatibility groups (VCGs), and there was no affinity between VCGs. Our results contribute to understanding FFSC and accurately identifying
spp. associated with the sugarcane crop.
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