Summary
Salicylic acid (SA) signalling plays an essential role in plant innate immunity. In this study, we identified a component in the SA signaling pathway in potato (Solanum tuberosum), the ...transcription factor StbZIP61, and characterized its function in defence against Phytophthora infestans. Expression of StbZIP61 was induced upon P. infestans infection and following exposure to the defense signaling hormones SA, ethylene and jasmonic acid. Overexpression of StbZIP61 increased the tolerance of potato plants to P. infestans while RNA interference (RNAi) increased susceptibility. Yeast two‐hybrid and pull down experiments revealed that StbZIP61 could interact with an NPR3‐like protein (StNPR3L) that inhibited its DNA‐binding and transcriptional activation activities. Moreover, StNPR3L interacted with StbZIP61 in an SA‐dependent manner. Among candidate genes involved in SA‐regulated defense responses, StbZIP61 had a significant impact on expression of StICS1, which encodes a key enzyme for SA biosynthesis. StICS1 transcription was induced upon P. infestans infection and this responsive expression to the pathogen was reduced in StbZIP61 RNAi plants. Accordingly, StICS1 expression was remarkably enhanced in StbZIP61‐overexpressing plants. Together, our data demonstrate that StbZIP61 functions in concert with StNPR3L to regulate the temporal activation of SA biosynthesis, which contributes to SA‐mediated immunity against P. infestans infection in potato.
Significance statement
The regulatory mechanism for dynamic biosynthesis of SA in plant immunity remains largely unknown. Here, we show that potato transcription factor StbZIP61 participates in defense against P. infestans by regulating SA biosynthesis. In response to pathogen infection, StbZIP61 promotes SA synthesis by inducing StICS1 expression and this activity is repressed by the NPR3‐like protein StNPR3L. Our results demonstrate that StbZIP61 functions in concert with StNPR3L to establish a temporal SA accumulation in immune responses.
In this study, we identified a defense-related major latex protein （MLP） from upland cotton （designated GhMLP28） and investigated its functional mechanism. GhMLP28 transcripts were ubiquitously ...present in cotton plants, with higher accumulation in the root. Expression of the GhMLP28 gene was induced by Verticillium dahliae inoculation and was responsive to defense signaling molecules, including ethylene, jas- monic acid, and salicylic acid. Knockdown of GhMLP28 expression by virus-induced gene silencing re- sulted in increased susceptibility of cotton plants to V. dahliae infection, while ectopic overexpression of GhMLP28 in tobacco improved the disease tolerance of the transgenic plants. Further analysis revealed that GhMLP28 interacted with cotton ethylene response factor 6 （GhERF6） and facilitated the binding of GhERF6 to GCC-box element. Transient expression assay demonstrated that GhMLP28 enhanced the tran- scription factor activity of GhERF6, which led to the augmented expression of some GCC-box genes. GhMLP28 proteins were located in both the nucleus and cytoplasm and their nuclear distribution was dependent on the presence of GhERF6. Collectively, these results demonstrate that GhMLP28 acts as a positive regulator of GhERF6, and synergetic actions of the two proteins may contribute substantially to protection against V. dahliae infection in cotton plants.
•High collaborative efficiency for both organics and Cu2+ removal was achieved.•High anodic and cathodic efficiencies and high power densities were achieved under the optimal operation ...parameters.•The optimal operation parameters were determined by linear sweep voltammetry.
Organic matters and copper ions can be collaboratively removed from wastewater using a microbial fuel cell (MFC). High collaborative efficiencies for both organic matter and copper ions removal have not been achieved yet in previous studies. We demonstrate here that high collaborative efficiencies can be achieved by designing reactor construction and selecting operational parameters based on the results of linear sweep voltammetry (LSV). When the MFC was constructed as 1:2 volume ratio of anode to cathode chamber and operated at optimal conditions, 83% COD removal and 87% copper ion removal were obtained at the same time. In addition, the Cu-MFC also performed a high coulombic efficiency (CE) of 89% for organic treatment, a cathodic efficiency of 80% for copper ion removal, and a maximum power density of 2.0W/m2.
Primary malignant melanoma of the esophagus (PMME) is an extremely rare but highly aggressive malignancy with a poor prognosis. Due to the scarcity of driver gene alterations, there is a need for ...more clinical data to comprehensively depict its molecular alterations. This study reviewed 26 PMME cases from three medical centers. Hybrid capture‐based targeted sequencing of 295 and 1021 genes was performed in 14 and 12 cases, respectively. We found that PMME patients had a relatively low tumor mutation burden (median, 2.88 mutations per Mb) and were simultaneously accompanied by mutations in genes such as KIT (6/26, 23%), TP53 (6/26, 23%), SF3B1 (4/26, 15%), and NRAS (3/26, 12%). KIT, NRAS, and BRAF were mutually exclusive, and SF3B1 co‐occurred with KIT mutation and amplification. The most common pathways affected were the mitogen‐activated protein kinases and DNA damage response (DDR) pathways. Stage IV was a risk factor for both progression‐free survival (hazard ratio HR = 5.14, 95% confidence interval CI = 1.32–19.91) and overall survival (OS), HR = 4.33, 95% CI = 1.22–15.30). Treatment with immune‐checkpoint inhibitors (ICIs) was an independent factor for favorable OS (HR = 0.10, 95% CI = 0.01–0.91). Overall, PMME is a complex malignancy with diverse gene alterations, especially with harboring DDR alterations for potentially response from ICIs.
Background
Identification of activated epidermal growth factor receptor (EGFR) mutations and application of EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs) have greatly changed the therapeutic strategies ...of non‐small‐cell lung cancer (NSCLC). However, the long‐term efficacy of EGFR‐TKI therapy is limited due to the development of drug resistance. The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR‐TKIs in advanced NSCLC patients with activated EGFR mutations.
Methods
We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR‐TKI treatment, from April 2004 and March 2011, at the Sun Yat‐sen University Cancer Center. Several genetic alterations associated with the efficacy of EGFR‐TKIs, including the alterations in BIM, ALK, KRAS, PIK3CA, PTEN, MET, IGF1R, and ROS1, were detected by the routine clinical technologies. The progression‐free survival (PFS) and overall survival (OS) were compared between different groups using Kaplan–Meier survival analysis with the log‐rank test. A Cox regression model was used to estimate multivariable‐adjusted hazard ratios (HRs) and their 95% confidence intervals (95% CIs) associated with the PFS and OS.
Results
Among the investigated patients, 169 NSCLC patients harbored EGFR‐sensitive mutations. EGFR‐mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN (P = 0.003 for PFS, and P = 0.034 for OS). In the combined molecular analysis of EGFR signaling pathway and resistance genes, we found that EGFR‐mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations (P < 0.001). A Cox proportional regression model determined that PTEN deletion (HR = 4.29,95% CI = 1.72–10.70) and low PTEN expression (HR = 1.96, 95% CI = 1.22–3.13), MET FISH + (HR = 2.83,95% CI = 1.37–5.86) were independent predictors for PFS in patients with EGFR‐TKI treatment after adjustment for multiple factor.
Conclusions
We determined that the coexistence of genetic alterations in cancer genes may explain primary resistance to EGFR‐TKIs.
Neuroblastoma (NB) is the most common and deadliest pediatric solid tumor. Targeting and reactivating tumor‐associated macrophages (TAMs) is necessary for reversing immune suppressive state and ...stimulating immune defense to exert tumoricidal function. However, studies on the function and regulation of TAMs in NB progression are still limited. Fatty acid binding protein 4 (FABP4) in TAMs was correlated with advanced clinical stages and unfavorable histology of NB. FABP4‐mediated macrophages increased migration, invasion, and tumor growth of NB cells. Mechanically, FABP4 could directly bind to ATPB to accelerate ATPB ubiquitination in macrophages. The consequently decreased ATP levels could deactivate NF‐κB/RelA‐IL1α pathway, which subsequently results in macrophages reprogrammed to an anti‐inflammatory phenotype. We also demonstrated that FABP4‐enhanced migration and invasion were significantly suppressed by IL1α blocking antibody. Furthermore, circulating FABP4 was also associated with the clinical stages of NB. Our findings suggest that FABP4‐mediated macrophages may promote proliferation and migration phenotypes in NB cells through deactivating NF‐κB‐IL1α pathway by ubiquitinating ATPB. This study reveals the pathologic and biologic role of FABP4‐mediated macrophages in NB development and exhibits a novel application of targeting FABP4 in macrophages for NB treatment.
FABP4 in macrophages expression is correlated with advanced clinical stages and unfavorable histology of neuroblastoma.
FABP4 in macrophages increases migration, invasion, and tumor growth of neuroblastoma cells.
FABP4 in macrophages may promote proliferation and migration phenotypes in neuroblastoma cells through deactivating NF‐κB‐IL1α pathway by ubiquitinating ATPB.
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