Transmission of synovial sarcoma from a single multi-organ donor to three transplant recipients: case report

Quick and reliable testing of EGFR and KRAS is needed in non-small cell lung cancer (NSCLC) to ensure optimal decision-making for targeted therapy. The Idylla™ platform was designed for Formalin-Fixed Paraffin-Embedded (FFPE) tissue sections but recently several studies were published that evaluated its potential for cytological specimens. This study aimed to validate the Idylla™ platform for the detection of EGFR/KRAS mutations in cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding. The KRAS Idylla™ test were performed on 11 specimens with a known KRAS mutation. The EGFR Idylla™ test was performed on 18 specimens with a known primary EGFR mutation and 7 specimens with a primary EGFR-EGFR T790M resistance mutation combination. Concordant KRAS and primary EGFR mutations were detected for both KRAS and primary EGFR mutations. Samples with a total CQ value of < 26 could be considered negative. Samples with a total CQ value of > 26 could not be assessed (probability of false-negative). In specimens with a primary EGFR-EGFR T790M resistance mutation combination, 5/7 cases were not concordant. Our results confirm the conclusion of recent reports that the Idylla™EGFR assay is not suitable in a resistance to EGFR TKI setting, also not in our cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding. KRAS and primary EGFR mutations were detected using the Idylla™ assays in virtually all cytological NSCLC samples. This analysis was rapid and time-saving compared to other mutation detection assays and may be useful if the amount of material is insufficient to perform a full set of molecular tests.     

Effects of growth-promoting rhizobacteria on maize growth and rhizosphere microbial community under conservation tillage in Northeast China

Conservation tillage in conjunction with straw mulching is a sustainable agricultural approach. However, straw mulching reduces the soil temperature, inhibits early maize growth and reduces grain yield in cold regions. To address this problem, we investigated the effects of inoculation of plant growth-promoting rhizobacteria (PGPR) on maize growth and rhizosphere microbial communities under conservation tillage in Northeast China. The PGPR strains Sinorhizobium sp. A15, Bacillus sp. A28, Sphingomonas sp. A55 and Enterobacter sp. P24 were isolated from the maize rhizosphere in the same area and inoculated separately. Inoculation of these strains significantly enhanced maize growth, and the strains A15, A28 and A55 significantly increased grain yield by as much as 22%–29%. Real-time quantitative PCR and high-throughput sequencing showed that separate inoculation with the four strains increased the abundance and species richness of bacteria in the maize rhizosphere. Notably, the relative abundance of Acidobacteria_Subgroup_6, Chloroflexi_KD4-96, and Verrucomicrobiae at the class level and Mucilaginibacter at the genus level were positively correlated with maize biomass and yield. Inoculation with PGPR shows potential for improvement of maize production under conservation tillage in cold regions by regulating the rhizosphere bacterial community structure and by direct stimulation of plant growth.     

MoSep3 and MoExo70 are needed for MoCK2 ring assembly essential for appressorium function in the rice blast fungus,Magnaporthe oryzae

Polar growth during appressorium formation is vital for the penetration peg formation in the rice blast fungus, Magnaporthe oryzae. Previous research has shown that the Sln1-septin-exocyst complex, localized at the base of the appressorium in contact with the leaf surface, forms a ring structure that influences growth polarity and affects penetration peg formation, and is necessary for pathogenicity. Our previous research showed CK2 proteins assemble another ring structure positioned perpendicular to the Sln1-septin-exocyst complex. Our research showed that the CK2 ring needs to become correctly assembled for penetration peg function and subsequent plant infection. In the present study, we found that the ring structures of CK2 are absent in the appressorium of ΔMoSep3 septin deletion mutants lacking the septin ring of the Sln1-septin-exocyst complex. Sln1 affects the septin proteins that recruit the exocyst complex that localizes as another ring at the appressorium's bottom. Destruction of the exocyst complex by mutation also causes incorrect localization of the CK2 ring structure. In conclusion, CK2 probably takes part in reestablishing the appressorium' spolarity growth necessary for penetration peg formation. We can also conclude that the correct localization and assembly of one or more CK2 ring structures in the appressorium depend on the initial assembly of the Sln1-septin-exocyst complex two rings at the base of the appressorium.     

Viral RNA-binding ability conferred by SUMOylation at PB1 K612 of influenza A virus is essential for viral pathogenesis and transmission

Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.     

Construction of a robust prognostic model for adult adrenocortical carcinoma: Results from bioinformatics and real-world data

This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large-scale multiomics analysis and real-world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis-related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI’s GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P < .001), TFRC (P < .001), TSC1 (P < .001) expression indicated significantly worse overall survival for adult ACC patients. Risk assessment suggested significantly a strong predictive capacity of IPRPs model for poor overall survival (P < .05). IPRPs model showed a little stronger ability for predicting prognosis than Ki-67 protein in FUSCC cohort (P = .003, HR = 3.947; P = .005, HR = 3.787). In external validation of IPRPs model using gene expression data, IPRPs model showed strong ability for predicting prognosis in TCGA cohort (P = .005, HR = 3.061) and it exhibited best ability for predicting prognosis in GSE10927 cohort (P = .0898, HR = 2.318). This research constructed IPRPs model for predicting adult ACC patients’ prognosis using proteomic data, gene expression data and real-world data and this prognostic model showed stronger predictive value than other biomarkers (Ki-67, Beta-catenin, etc) in multi-cohorts.     

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.     

Allelopathic effects of switchgrass on redroot pigweed and crabgrass growth

Non-native invasive plant species influence plant community composition and competitively eradicate native species. However, there is doubt regarding how global invasive species increase and explosively interfere with native plants. Invasive plants always have strong allelopathic potential. In this study, allelopathic effects of switchgrass on redroot pigweed and crabgrass growth were investigated by field and laboratory experiments. Within a 0.4-m distance of switchgrass, density and shoot biomass of native species were significantly suppressed in the field, with 95.1% and 93.0% inhibition on density of redroot pigweed and crabgrass and with 99.0% and 97.7% inhibition on shoot biomass, respectively, during the third growing season. Significant inhibitory effects on shoot and root biomass were observed at the 5:5 (switchgrass–native species) proportion in glass bottles, by 41.57% and 51.21% for shoot and root biomass of redroot pigweed and by 33.42% and 56.95% for shoot and root biomass of crabgrass, respectively. Results of a glass bottle experiment showed that shoot and root biomass of redroot pigweed and crabgrass could be significantly inhibited by contact with switchgrass root. Results of a Petri dish experiment showed that aqueous extracts of switchgrass significantly inhibited germination process of both species at high concentrations, with 90.74% and 18.62% inhibition on germination rate and plumule length of redroot pigweed and with 63.59%, 16.38%, and 19.92% inhibition on germination rate, plumule, and radicle lengths of crabgrass, respectively, at the concentration of 0.1 g·mL^?1. This report demonstrated that switchgrass had allelopathic effects on redroot pigweed and crabgrass growth.

     

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.