RESUMEN
Clear cell renal cell carcinoma (ccRCC), a prevalent kidney cancer form characterised by its invasiveness and heterogeneity, presents challenges in late-stage prognosis and treatment outcomes. Programmed cell death mechanisms, crucial in eliminating cancer cells, offer substantial insights into malignant tumour diagnosis, treatment and prognosis. This study aims to provide a model based on 15 types of Programmed Cell Death-Related Genes (PCDRGs) for evaluating immune microenvironment and prognosis in ccRCC patients. ccRCC patients from the TCGA and arrayexpress cohorts were grouped based on PCDRGs. A combination model using Lasso and SuperPC was constructed to identify prognostic gene features. The arrayexpress cohort validated the model, confirming its robustness. Immune microenvironment analysis, facilitated by PCDRGs, employed various methods, including CIBERSORT. Drug sensitivity analysis guided clinical treatment decisions. Single-cell data enabled Programmed Cell Death-Related scoring, subsequent pseudo-temporal and cell-cell communication analyses. A PCDRGs signature was established using TCGA-KIRC data. External validation in the arrayexpress cohort underscored the model's superiority over traditional clinical features. Furthermore, our single-cell analysis unveiled the roles of PCDRG-based single-cell subgroups in ccRCC, both in pseudo-temporal progression and intercellular communication. Finally, we performed CCK-8 assay and other experiments to investigate csf2. In conclusion, these findings reveal that csf2 inhibit the growth, infiltration and movement of cells associated with renal clear cell carcinoma. This study introduces a PCDRGs prognostic model benefiting ccRCC patients while shedding light on the pivotal role of programmed cell death genes in shaping the immune microenvironment of ccRCC patients.
Asunto(s)
Carcinoma de Células Renales , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Aprendizaje Automático , Microambiente Tumoral , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Microambiente Tumoral/genética , Pronóstico , Neoplasias Renales/genética , Neoplasias Renales/patología , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Apoptosis/genética , Análisis de la Célula Individual/métodosRESUMEN
Valsa pyri-induced pear Valsa canker is among the most prevalent diseases to impact pear quality and yields. Biocontrol strategies to control plant disease represent an attractive alternative to the application of fungicides. In this study, the potential utility of Bacillus atrophaeus strain HF1 was assessed as a biocontrol agent against pear Valsa canker. Strain HF1 suppressed V. pyri mycelium growth by 61.20% and induced the development of malformed hyphae. Both culture filtrate and volatile organic compounds (VOCs) derived from strain HF1 were able to antagonize V. pyri growth. Treatment with strain HF1-derived culture filtrate or VOCs also induced the destruction of hyphal cell membranes. Headspace mixtures prepared from strain HF1 were analyzed, leading to the identification of 27 potential VOCs. Of the thirteen pure chemicals tested, iberverin, hexanoic acid, and 2-methylvaleraldehyde exhibited the strongest antifungal effects on V. pyri, with respective EC50 values of 0.30, 6.65, and 74.07 µL L-1. Fumigation treatment of pear twigs with each of these three compounds was also sufficient to prevent the development of pear Valsa canker. As such, these results demonstrate that B. atrophaeus strain HF1 and the volatile compounds iberverin, hexanoic acid, and 2-methylvaleraldehyde exhibit promise as novel candidate biocontrol agents against pear Valsa canker.
Asunto(s)
Ascomicetos , Pyrus , Pyrus/microbiología , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiologíaRESUMEN
Botryosphaeria dothidea causes white rot, which is among the most devastating diseases affecting apple crops globally. In this study, we assessed B. dothidea resistance to carbendazim by collecting samples from warts on the infected branches of apple trees or from fruits exhibiting evidence of white rot. All samples were collected from different orchards in nine provinces of China in 2018 and 2019. In total, 440 B. dothidea isolates were evaluated, of which 19 isolates from three provinces were found to exhibit carbendazim resistance. We additionally explored the fitness and resistance stability of these isolates, revealing that they were no less fit than carbendazim-sensitive isolates in terms of pathogenicity, sporulation, and mycelial growth and that the observed carbendazim resistance was stable. Sequencing of the ß-tubulin gene in carbendazim-resistant isolates showed the presence of a substitution at codon 198 (GAG to GCG) that results in an alanine substitution in place of glutamic acid (E198A) in all 19 resistant isolates. A loop-mediated isothermal amplification (LAMP) method was then developed to rapidly and specifically identify this E198A mutation. This LAMP method offers value as a tool for rapidly detecting carbendazim-resistant isolates bearing this E198A mutation and can thus be used for the widespread monitoring of apple crops to detect and control the development of such resistance.
Asunto(s)
Ascomicetos , Malus , Ascomicetos/genética , Bencimidazoles , Carbamatos/farmacologíaRESUMEN
The heterotrimeric G proteins play an essential role in a wide variety of signal transduction pathways, mediating the process of chemical signals from the environment in all higher eukaryotic organisms. In this article, two G-protein subunit genes encoding Gαq and Gß1 were cloned from Bemisia tabaci Gennadius. The full-length cDNA sequence of BtGαq consisted of 2,336 bp with an ORF of 1,062 bp encoding 353 amino acids and BtGß1 had a full length of 1,942 bp with an ORF of 1,023 nucleotides encoding 340 amino acids. The amino acid sequences of BtGαq and BtGß1 from B. tabaci B biotype were identical to those from the Q biotype. Phylogenetic analysis identified G protein α and ß subunit families from insects based on their amino acid sequences. The expression patterns of BtGαq and BtGß1 at different development stages and in different body regions were analyzed by real-time quantitative PCR and Western blot. The results show that BtGαq and BtGß1 are neither developmental stage-specific nor tissue-specific. The transcript levels of BtGαq in the B biotype are similar to that in the Q biotype, the transcript levels of BtGß1 at egg, first instar and pupae in B biotype were significantly higher than that in Q biotype. The transcript levels of BtGαq and BtGß1 in the head were significantly higher than those in thorax and abdomen indicating that they are involved in nervous system and sensory functions.
Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades beta de la Proteína de Unión al GTP/genética , Hemípteros/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Western Blotting , Clonación Molecular , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/biosíntesis , Subunidades beta de la Proteína de Unión al GTP/biosíntesis , Regulación del Desarrollo de la Expresión Génica , Hemípteros/metabolismo , Masculino , Datos de Secuencia Molecular , Filogenia , ARN/química , ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Valsa canker caused by Valsa pyri is one of the most destructive diseases of pear, leading to severe yield and economic losses. Volatile organic compounds (VOCs) from endophytes have important roles in the regulation of plant disease. In this study, we investigated the biocontrol activity of the endophytic fungus Aspergillus niger strain La2 and its antagonistic VOCs against pear Valsa canker. RESULTS: Strain La2 exhibited an obvious inhibitory effect against V. pyri. A colonization assay suggested that strain La2 could complete its life cycle on pear twigs. The symptoms of pear Valsa canker were weakened on detached pear twigs after treatment with strain La2. In addition, VOCs from strain La2 also significantly suppressed mycelial growth in V. pyri. Based on the results of headspace solid-phase microextraction/gas chromatography-mass spectrometry analysis, six possible VOCs produced by strain La2 were detected, of which 2,4-di-tert-butylphenol and 4-methyl-1-pentanol were the main antagonistic VOCs in terms of their effect on pear Valsa canker in vitro and in vivo. Further results showed that 4-methyl-1-pentanol could destroy the V. pyri hyphal structure and cell membrane integrity. Importantly, the activities of pear defense-related enzymes (polyphenol oxidase, phenylalanine ammonia lyase and superoxide dismutase) were enhanced after 4-methyl-1-pentanol treatment in pear twigs, suggesting that 4-methyl-1-pentanol might induce a plant disease resistance response. CONCLUSION: Aspergillus niger strain La2 and its VOCs 2,4-di-tert-butylphenol and 4-methyl-1-pentanol have potential as novel biocontrol agents of pear Valsa canker. © 2024 Society of Chemical Industry.
Asunto(s)
Aspergillus niger , Enfermedades de las Plantas , Pyrus , Compuestos Orgánicos Volátiles , Pyrus/microbiología , Compuestos Orgánicos Volátiles/farmacología , Compuestos Orgánicos Volátiles/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Endófitos/fisiología , Agentes de Control Biológico/farmacologíaRESUMEN
The biochemical recurrence (BCR) of patients with prostate cancer (PCa) after radical prostatectomy is high, and mitochondrial respiration is reported to be associated with the metabolism in PCa development. This study aimed to establish a mitochondrial respiratory gene-based risk model to predict the BCR of PCa. RNA sequencing data of PCa were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and mitochondrial respiratory-related genes (MRGs) were sourced via GeneCards. The differentially expressed mitochondrial respiratory and BCR-related genes (DE-MR-BCRGs) were acquired through overlapping BCR-related differentially expressed genes (BCR-DEGs) and differentially expressed MRGs (DE-MRGs) between PCa samples and controls. Further, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were performed to construct a DE-MRGs-based risk model. Then, a nomogram was established by analyzing the independent prognostic factor of five clinical features and risk scores. Moreover, Gene Set Enrichment Analysis (GSEA), tumor microenvironment, and drug susceptibility analyses were employed between high- and low-risk groups of PCa patients with BCR. Finally, qRT-PCR was utilized to validate the expression of prognostic genes. We identified 11 DE-MR-BCRGs by overlapping 132 DE-MRGs and 13 BCR-DEGs and constructed a risk model consisting of 4 genes (APOE, DNAH8, EME2, and KIF5A). Furthermore, we established an accurate nomogram, including a risk score and a Gleason score, for the BCR prediction of PCa patients. The GSEA result suggested the risk model was related to the PPAR signaling pathway, the cholesterol catabolic process, the organic hydroxy compound biosynthetic process, the small molecule catabolic process, and the steroid catabolic process. Simultaneously, we found six immune cell types relevant to the risk model: resting memory CD4+ T cells, monocytes, resting mast cells, activated memory CD4+ T cells, regulatory T cells (Tregs), and macrophages M2. Moreover, the risk model could affect the IC50 of 12 cancer drugs, including Lapatinib, Bicalutamide, and Embelin. Finally, qRT-PCR showed that APOE, EME2, and DNAH8 were highly expressed in PCa, while KIF5A was downregulated in PCa. Collectively, a mitochondrial respiratory gene-based nomogram including four genes and one clinical feature was established for BCR prediction in patients with PCa, which could provide novel strategies for further studies.
RESUMEN
Glutamine has been recognized as an important amino acid that provide a variety of intermediate products to fuel biosynthesis. Glutamine metabolism participates in the progression of the tumor via various mechanisms. However, glutamine-metabolism-associated signatures and its significance in prostate cancer are still unclear. In this current study, we identified five genes associated with glutamine metabolism by univariate and Lasso regression analysis and constructed a model to predict the biochemical recurrence free survival (BCRFS) of PCa. Further validation of the prognostic risk model demonstrated a good efficacy in predicting the BCRFS in PCa patients. Interestingly, based on the CIBERSORTx, ssGSEA and ESTIMATE algorithms predictions, we noticed a distinct immune cell infiltration and immune pathway pattern in the prediction of the two risk groups stratified by the risk model. Drug sensitivity prediction revealed that patients in the high-risk group were more suitable for chemotherapy. Last but not least, glutamine deprivation significantly inhibited cell growth in GLUL or ASNS knock down prostate cancer cell lines. Therefore, we proposed a novel prognostic model by using glutamine metabolism genes for PCa patients and identified potential mechanism of PCa progression through glutamine-related tumor microenvironment remodeling.
RESUMEN
Background: Presently, a comprehensive analysis of integrin subunit genes (ITGs) in bladder cancer (BLCA) is absent. This study endeavored to thoroughly analyze the utility of ITGs in BLCA through computer algorithm-based bioinformatics. Methods: BLCA-related materials were sourced from reputable databases, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). R software-based bioinformatics analyses included limma-differential expression analysis, survival-Cox analysis, glmnet-Least absolute shrinkage and selection operator (LASSO), clusterProfiler-functional annotation, and gsva-estimate-immune landscape analysis. The expression difference of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Among the 11 ITGs that were abnormally expressed in BLCA, ITGA7, ITGA5, and ITGB6 were categorized as the optimal variables for structuring the risk model. The high-risk subcategories were typified by brief survival, abysmal prognosis, prominent immune and stromal markers, and depressed tumor purity. The risk model was also an isolated indicator of the impact of clinical outcomes in BLCA patients. Moreover, the risk model, specifically the high-risk subcategory with inferior prognosis, became heavily interlinked with the immune-inflammatory response and smooth muscle contraction and relaxation. Conclusion: This study determined three ITGs with prognostic values (ITGA7, ITGA5, and ITGB6), composed a novel (ITG-associated) prognostic gene signature, and preliminarily probed the latent molecular mechanisms of the model.
RESUMEN
Introduction: Obesity is generally thought to increase the difficulty and complications of surgery. Laparoscopic adrenalectomy has become the standard operation for adrenal tumors at present. Aim: To assess whether laparoscopic adrenalectomy (LA) can be used for obese patients with adrenal tumor. Material and methods: We systematically searched PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Science databases and Cochrane Library, and the search time is up to January 2022. We used STATA 16.0 and RevMan 5.4 software for data processing and statistical analysis. Results: Eight studies were included in the meta-analysis. The meta-analysis results showed that compared with the nonobese group, the obese group had a significantly longer operation time (OT) (weighted mean difference (WMD): -10.02, 95% confidence interval (CI): -19.16 to 0.87, p = 0.03). It also had higher estimated blood loss (WMD: -13.15, 95% CI: -35.92 to 9.63, p = 0.26) and conversion rate (odds ratio (OR): 0.70, 95% CI: 1.31 to 1.60, p = 0.40), longer length of hospital stay (LOS) (WMD: -0.04, 95% CI: -0.47 to 0.39, p = 0.86), and a higher number of complications (odds ratio (OR) = 0.71, 95% CI: 0.49 to 1.02, p = 0.06), but these differences were not statistically significant. Additionally, in subgroup analysis longer OT (p = 0.0001) and LOS (p = 0.007) were associated with retroperitoneal laparoscopic adrenalectomy for obesity. Conclusions: Our meta-analysis suggests that LA is feasible and effective in patients with obesity.
RESUMEN
Apple ring rot, one of the most common apple postharvest diseases during storage, is caused by Botryosphaeria dothidea. Fungicide application is the most widely used method to control this disease, but the increasing environmental and food safety concerns greatly limit their use. The present study aimed to examine the biocontrol activity and underlying action mechanism of Bacillus halotolerans strain Pl7 against B. dothidea. The results revealed that B. halotolerans strain Pl7 exhibited strong inhibitory activity against B. dothidea by 69% in vitro. The culture filtrate of strain Pl7 possessed cellulase, ß-1, 3-glucanase, protease activity and mediated the antifungal activity against B. dothidea. Further analysis demonstrated that culture filtrate of strain Pl7 could cause cell membrane permeabilization of B. dothidea. Apple fruit suffering from ring rot induced by a carbendazim (CBZ)-sensitive or -resistant B. dothidea isolate was much suppressed after being treated with strain Pl7, maintaining postharvest quality. The ability of strain Pl7 to swiftly colonize and thrive in apple fruit wounds was demonstrated by a re-isolation assay. Additional transcriptome studies of untreated and treated apple fruit with strain Pl7 revealed that strain Pl7 mostly changed the expression of genes functioning in plant secondary metabolite biosynthesis and plant-pathogen interaction. In light of these outcomes, the underlying antagonistic mechanism was investigated, and B. halotolerans strain Pl7 was identified as a promsing microbial biocontrol agent against apple postharvest decay.
RESUMEN
Pear Valsa canker caused by Valsa pyri is among the most destructive diseases of pear, which causes significant economic loss. The present study was developed to explore the biocontrol efficiency and underlying antagonistic mechanism of Paenibacillus polymyxa strain Nl4 against V. pyri. P. polymyxa strain Nl4, one of the 120 different endophytic bacterial strains from pear branches, exhibited strong inhibitory effects against the mycelial growth of V. pyri and caused hyphal malformation. Culture filtrate derived from strain Nl4 was able to effectively suppress mycelial growth of V. pyri, and was found to exhibit strong protease, cellulase and ß-1, 3-glucanase activity. Through re-isolation assay, strain Nl4 was confirmed to be capable of colonizing and surviving in pear branch. Treatment with strain NI4 effectively protected against pear Valsa canker symptoms on detached pear twigs inoculated with V. pyri. Moreover, strain Nl4 promoted enhanced plant growth probably through the solubilization of phosphorus. Comparative transcriptomic analyses revealed that strain NI4 was able to suppress V. pyri growth in large part through the regulation of the expression of membrane- and energy metabolism-related genes in this pathogen. Further transcriptomic analyses of pear trees indicated that strain NI4 inoculation was associated with changes in the expression of genes associated with secondary metabolite biosynthesis, signal transduction, and cutin, suberine, and wax biosynthesis. Together, these data highlighted P. polymyxa strain Nl4 as a promising biocontrol agent against pear Valsa canker and investigated the possible mechanisms of strain Nl4 on control of this devastating disease.
RESUMEN
Kiwifruit is very popular among consumers due to its high nutritional value. The increasing expansion in kiwifruit cultivation has led to the spread of rot diseases. To identify the pathogens causing kiwifruit ripe rots in China, 24 isolates were isolated from the diseased fruit and wart in trees. Botryosphaeria dothidea was recognized as the pathogen causing kiwifruit ripe rot and wart in the tree through internal transcribed spacer (ITS) sequencing, pathogenicity testing, morphological and microscopic characteristics. The rapid and accurate detection of this pathogen will lead to better disease monitoring and control efforts. A loop-mediated isothermal amplification (LAMP) method was then developed to rapidly and specifically identify B. dothidea. These results offer value to further research into kiwifruit ripe rot, such as disease prediction, pathogen rapid detection, and effective disease control.
RESUMEN
Botryosphaeria dothidea causes apple ring rot, which is among the most prevalent postharvest diseases of apples and causes significant economic loss during storage. In this study, we investigated the biocontrol activity and possible mechanism of Bacillus velezensis strain P2-1 isolated from apple branches against B. dothidea in postharvest apple fruit. The results showed strain P2-1, one of the 80 different endophytic bacterial strains from apple branches, exhibited strong inhibitory effects against B. dothidea growth and resulted in hyphal deformity. B. velezensis P2-1 treatment significantly reduced the ring rot caused by B. dothidea. Additionally, the supernatant of strain P2-1 exhibited antifungal activity against B. dothidea. Re-isolation assay indicated the capability of strain P2-1 to colonize and survive in apple fruit. PCR and qRT-PCR assays revealed that strain P2-1 harbored the gene clusters required for biosynthesis of antifungal lipopeptides and polyketides. Strain P2-1 treatment significantly enhanced the expression levels of pathogenesis-related genes (MdPR1 and MdPR5) but did not significantly affect apple fruit qualities (measured in fruit firmness, titratable acid, ascorbic acid, and soluble sugar). Thus, our results suggest that B. velezensis strain P2-1 is a biocontrol agent against B. dothidea-induced apple postharvest decay. It acts partially by inhibiting mycelial growth of B. dothidea, secreting antifungal substances, and inducing apple defense responses.
RESUMEN
Pomegranate fruit rot caused by Coniella granati is among the most devastating diseases threatening pomegranate production. The pathogenic mechanism of this pathogen remains largely unknown due to lack of genetic transformation method. Herein, we developed an approach to the Agrobacterium tumefaciens-mediated transformation (ATMT) of C. granati using a plasmid vector encoding the green fluorescent protein (GFP) and hygromycin resistance (Hyg) genes. This approach yielded C. granati transformants that exhibited uniform, stable green fluorescence. We further optimized this ATMT protocol, enabling us to achieve a transformation efficiency of up to 300 transformants per 0.5 cm2 mycelial plug. Together, we thus provide the first report of the stable transformation of C. granati, laying a foundation for future functional studies characterizing this economically important fungal pathogen.
Asunto(s)
Ascomicetos , Micosis/microbiología , Enfermedades de las Plantas/microbiología , Granada (Fruta)/microbiología , Ascomicetos/genética , Ascomicetos/crecimiento & desarrollo , ADN Bacteriano/genética , Vectores Genéticos , Proteínas Fluorescentes Verdes/genética , Mutagénesis Insercional , Transformación GenéticaRESUMEN
Y-tube olfactometer and net cages experiments were used to investigate the repellent effects of different celery varieties in biotype Q of sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), on cucumber, Cucumis sativus L. (Cucurbitaceae). Y-tube olfactometer tests showed that whiteflies have strong repellent behavior to different celery varieties. Intercropping different celery varieties with cucumbers had significant repellent effects and oviposition deterrent effects in whiteflies. Results obtained demonstrated that the Western Europe celery varieties, Juventus and Ventura, and the Chinese celery variety, Jinnan, had good repellent efficacy against the whitefly. D-Limonene, ß-myrcene, and (E)-ß-ocimene might be the main active components in celery that affected the selection behavior of B. tabaci. In Western Europe celery varieties, D-limonene was the main volatile component for the repellent effects in B. tabaci; however, the two Chinese celery varieties that showed repellent effects had relatively higher volatilization quantities of ß-myrcene than of D-limonene.
Asunto(s)
Antibiosis , Apium/química , Producción de Cultivos , Cucumis sativus/crecimiento & desarrollo , Hemípteros/fisiología , Animales , Repelentes de Insectos/farmacología , Olfatometría , Compuestos Orgánicos Volátiles/farmacologíaRESUMEN
Based on data obtained from 572 branches of 45 Chinese fir trees in Jiangle Forest Farm, Fujian Province, southeast China, prediction models for branch, foliage biomass and total branch and foliage biomass of individual tree were developed by linear mixed effects (LME) method, and tested by independent samples. The results showed that the LME models provided better performance than the multiple linear regression models for the branch, foliage and total biomass prediction of Chinese fir plantation. The LME models with different combinations of the random effects parameters had different fitting precisions. The LME models including variance structures could effectively remove the heteroscedasticity in the data and improved the precision. The LME model with the exponential function as the variance structure had better fitting precisions for the total biomass and foliage biomass models, and that with the constant plus power function as the variance structure had better performance for the branch biomass model. Model validation confirmed that the LME models with the random effects and heteroscedasticity structure could significantly improve the precision of prediction, compared to the multiple linear regression models.