Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children's Oncology Group study AALL0433 evaluated a new platform for relapsed ...ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93.8 +/- 2.7% for patients with MRD <0.1%, vs. 53.7 +/- 7.8% and 60.6 +/- 7.8% for patients with MRD ≥0.1% (p<0.0001). Patients who received HCT vs. chemotherapy alone had an improved 3-year disease-free survival (77.5 +/- 6.2% vs. 66.9 +/- 4.5%, p=0.03) but not OS (81.5 +/- 5.8% for HCT vs. 85.8 +/- 3.4% for chemotherapy, p=0.46). Patients with early iCNS relapse fared poorly, with a 3-year EFS/OS of 41.4% +/- 9.2% and 51.7% +/- 9.3%, respectively. Infectious toxicities of the chemotherapy platform were significant. The AALL0433 chemotherapy platform is efficacious for late bone marrow relapse of B-ALL, but with significant toxicities. The MRD threshold of 0.1% at the end of Induction-1 was highly predictive of outcome. The optimal role for HCT for this patient population remains uncertain. This trial is registered at clinicaltrials.gov (NCT# 00381680).
Geometric similarity plays an important role in geographic information retrieval, map matching, and data updating. Many approaches have been developed to calculate the similarity between simple ...features. However, complex group objects are common in map and spatial database systems. With a micro scene that contains different types of geographic features, calculating similarity is difficult. In addition, few studies have paid attention to the changes in a scene’s geometric similarity in the process of generalization. In this study, we developed a method for measuring the geometric similarity of micro scene generalization based on shape, direction, and position. We calculated shape similarity using the hybrid feature description, and we constructed a direction Voronoi diagram and a position graph to measure the direction similarity and position similarity. The experiments involved similarity calculation and quality evaluation to verify the usability and effectiveness of the proposed method. The experiments showed that this approach can be used to effectively measure the geometric similarity between micro scenes. Moreover, the proposed method accounts for the relationships amongst the geometrical shape, direction, and position of micro scenes during cartographic generalization. The simplification operation leads to obvious changes in position similarity, whereas delete and merge operations lead to changes in direction and position similarity. In the process of generalization, the river + islands scene changed mainly in shape and position, the similarity change in river + lakes occurred due to the direction and location, and the direction similarity of rivers + buildings and roads + buildings changed little.
Among the geographic elements, shape recognition and classification is one of the im portant elements of map cartographic generalization, and the shape classification of an areal settlement is an ...important part of geospatial vector data. However, there is currently no relatively simple and efficient way to achieve areal settlement classification. Therefore, we combined the skeleton line vector data of an areal settlement and the graph convolutional neural network to propose an areal settlement shape classification method that (1) extracts the skeleton line of the areal settlement to form a dual graph with nodes as edges, (2) extracts multiple features to obtain a graph representation of the shape, (3) extracts and aggregates the shape information represented by the areal settlement skeleton line using the graph convolutional neural network for multiple rounds to extract high-dimensional shape information, and (4) completes the shape classification of the high-dimensional shape information. The experiment used 240 samples, and the classification accuracy was 93.3%, with areal settlement shapes of E-, F-, and H-type achieving F-measures of 96.5%, 92.3%, and 100%, respectively. The result shows that the classification method of the areal settlement shape has high accuracy.
Analyzing the transcriptome of maize leaves under drought stress and rewatering conditions revealed that transcription factors were involved in this process, among which
of the ABSCISIC ...ACID-INSENSITIVE 5-like protein 5 family was induced to significantly up-regulated. The functional mechanism of
in Abscisic acd (ABA) signaling pathway and its response to drought stress and rewatering has not been studied yet. The present study found that ZmbZIP33 contains a DNA-binding and dimerization domain, has transcriptional activation activity, and is highly homologous to SbABI1,SitbZIP68 and OsABA1. The expression of
is strongly up-regulated by drought, high salt, high temperature, and ABA treatments. Overexpression of
remarkably increased chlorophyll content and root length after drought stress and rewatering, and, moreover, cause an accumulation of ABA content, thereby improving drought resistance and recovery ability in
. However, silencing the expression of
(BMV-ZmbZIP33) remarkably decreased chlorophyll content, ABA content, superoxide dismutase and peroxidase activities, and increased stomatal opening and water loss rate compared with BMV (control). It showed that silencing
lead to reduced drought resistance and recovery ability of maize. ABA sensitivity analysis found that 0.5 and 1 μmol/L treatments severely inhibited the root development of overexpression
transgenic
. However, the root growth of BMV was greatly inhibited for 1 and 5μmol/L ABA treatments, but not for BMV-ZmbZIP33. Subcellular localization, yeast two-hybrid and BIFC further confirmed that the core components of ABA signaling pathways ZmPYL10 and ZmPP2C7 interacted in nucleus, ZmPP2C7 and ZmSRK2E as well as ZmSRK2E and ZmbZIP33 interacted in the plasma membrane. We also found that expression levels of
and
in the BMV-ZmbZIP33 mutant were lower than those of BMV, while
was the opposite under drought stress and rewatering. However, expression of
and
in normal maize leaves were significantly up-regulated by 3-4 folds after drought and ABA treatments for 24 h, while
was down-regulated. The
and
encoding key enzymes in ABA biosynthesis are up-regulated in overexpression
transgenic line under drought stress and rewatering conditions, but down-regulated in BMV-ZmbZIP33 mutants. Together, these findings demonstrate that
played roles in ABA biosynthesis and regulation of drought response and rewatering in
and maize thought an ABA-dependent signaling pathway.
Abstract
Background
Lung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) serve as tumor promoters or suppressors in ...the development of various human malignancies, including LUAD. Although long intergenic non-protein coding RNA 1089 (LINC01089) suppresses the progression of breast cancer, its mechanism in LUAD requires further exploration. Thus, we aimed to investigate the underlying function and mechanism of LINC01089 in LUAD.
Methods
The expression of LINC01089 in LUAD and normal cell lines was detected. Functional assays were applied to measure cell proliferation, apoptosis and migration. Besides, mechanism experiments were employed for assessing the interplay among LINC01089, miR-301b-3p and StAR related lipid transfer domain containing 13 (STARD13). Data achieved in this study was statistically analyzed with Student’s
t
test or one-way analysis of variance.
Results
LINC01089 expression was significantly down-regulated in LUAD tissues and cells and its overexpression could reduce cell proliferation and migration. Moreover, LINC01089 could regulate STARD13 expression through competitively binding to miR-301b-3p in LUAD. Additionally, rescue assays uncovered that STARD13 depletion or miR-301b-3p overexpression could countervail the restraining effect of LINC01089 knockdown on the phenotypes of LUAD cells.
Conclusion
LINC01089 served as a tumor-inhibitor in LUAD by targeting miR-301b-3p/STARD13 axis, providing an innovative insight into LUAD therapies.
Trial registration
Not applicable.
Objective-To determine prognostic factors for and compare outcome among dogs with oral malignant melanoma following excision with or without various systemic adjuvant therapies. Design-Retrospective ...case series.Animals-151 dogs with naturally occurring oral malignant melanomas treated by excision with or without adjuvant therapies from 2001 to 2012. Procedures-Case accrual was solicited from Veterinary Society of Surgical Oncology members via an email list service. Information collected from case records included signalment, tumor staging, tumor characteristics, type of surgical excision, histologic diagnosis, adjuvant therapy, and survival time. Results-The overall median survival time was 346 days. Results of multivariate analysis indicated that tumor size, patient age, and intralesional excision (vs marginal, wide, or radical excision) were considered poor prognostic indicators. All other demographic and clinical variables were not significantly associated with survival time after adjusting for the aforementioned 3 variables. A clear survival benefit was not evident with any systemic adjuvant therapy, including vaccination against melanoma or chemotherapy; however, the number of dogs in each treatment group was small. Ninety-eight dogs received no postoperative adjuvant therapy, and there was no difference in survival time between dogs that did (335 days) and did not (352 days) receive systemic adjuvant therapy. Conclusions and Clinical Relevance-For dogs with oral malignant melanoma, increasing tumor size and age were negative prognostic factors. Complete excision of all macroscopic tumor burden improved survival time. Long-term survival was possible following surgery alone. Although systemic adjuvant therapy was not found to improve survival time, this could have been due to type II error.
To study the horizontal vibration characteristics of high-speed elevators, a 6-DOF horizontal dynamic model of the nonlinear coupling system of guide rails, guide shoes, and elevator cabin was ...established. Four kinds of guide rail excitation models, namely, sinusoidal, triangular, stepped, and pulsed excitation, were established through an error and contact analysis of guide rails and rollers. The factors that influenced the horizontal vibration response, such as excitation models, stiffness of guide shoes, and cabin parameters, were analyzed by solving the vibration acceleration of the coupling system. Vibration acceleration was measured through experiments to verify the theoretical results. The vibration acceleration of the no-load elevator under stepped excitation was the largest. Reducing the stiffness of the guide shoes and straightness error of guide rails, reasonably arranging the spacing between the guide shoes at the top and bottom of the cabin, and increasing the cabin weight were beneficial to reducing the horizontal vibration response of the elevator cabin.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
: Foliar pathogen infection can induce the enrichment of beneficial microbial consortia in plant rhizosphere, but the mechanism for enhanced plant resistance is unclear.
: We investigated the effects ...of foliar pathogen infection on bacterial communities in maize rhizosphere using high throughput sequencing.
: Maize plants grown in non-sterilized soils displayed stronger defense against the foliar pathogen
than those in sterilized soils. Foliar pathogen infection further triggered the shift in the structure and composition of rhizosphere bacterial communities. The pathogen-infected plants specially promoted rhizosphere colonization of several bacterial taxa. The
genus increased in the rhizosphere after pathogen infection. Other bacterial genera such as
and
were also greatly enriched in the rhizosphere of pathogen-infected plants. Furthermore, the enriched bacterial species were isolated and were shown to interact synergistically to promote biofilm formation. Although both the
and
species did not induce plant defense, the
species markedly increased the resistance of plants against
. Furthermore, the consortium consisting of the
,
and
species (CON
) conferred long-acting disease resistance of maize plants as compared to the individual
species. Furthermore, the inoculation with the CON
significantly induced a marked increase in the levels of DIMBOA in maize leaves, indicating that the consortium-induced increases of DIMBOA levels partially contributed to enhancing disease resistance of plants.
: Foliar infection of maize plants by
specifically recruited a group of beneficial rhizosphere bacteria, which conferred enhanced plant defense against pathogen infection. This study provided important evidence that above-ground pathogen infection participated in the mediation of below-ground microbiome for regulating plant defense systems.
Background
Enhancer RNAs (eRNAs), the transcriptional products of active enhancers, are of great significance in the initial progression of cancers. However, the biological function and ...bioinformatics profiles of eRNA in gastric cancer remains largely enigmatic.
Methods
Firstly, STAD were clustered into three subtypes with the data of eRNA expression from TCeA. Then we explored the difference of the tumor immune microenvironment, transcription levels, and transcription regulation among the three clusters. Finally, samples collected from 12 patients diagnosed with STAD were used to conduct qRT‐PCR, verifying the conclusion based on network database.
Results
The three clusters were detected to have different tumor microenvironments: Cluster A has an immune “cold” microenvironment. While cluster B features as more infiltration of immune cells, accompanied with higher expression of immune checkpoints such as PDCD1, LAG3, and TIGIT. Besides, Cluster C shows a higher stromal feature with B lineage, neutrophils, and fibroblasts. Further analyses indicated that CpG island methylation level of Cluster B is different from the other two clusters. Meanwhile, Cluster A and B showed significant enrichment of TP53 and KRAS mutation respectively while Cluster C has higher tumor mutation burden (TMB) and microsatellite instability (MSI). With the elaboration of transcriptional regulation of epigenetic clustering, we detected that Cluster A enriched in epithelial phenotype pathways. Cluster B enriched in cell–cell adhesion. Cluster C enriched in fibroblast proliferation. The clinical cohort show that Cluster B patients have lower interstitial cell characteristics and CAF infiltration.
Conclusion
We identified three unique epigenetic clusters of STAD through the differential activation of super‐enhancers, and identified Cluster B with a higher immune infiltrating and a better prognosis, which provides a novel understanding of eRNAs and potential clinical applicability of eRNA‐based molecular subtypes in gastric cancer.
We explored the landscape of eRNA and identified three subtypes with different immune status, genetic alternation, and epigenetic clusters, which provided eRNA‐based prognostic biomarkers and novel understanding in molecular carcinogenesis.
Full text
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The prevalence of non-alcoholic fatty liver disease (NAFLD) and its related mortality is increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for ...early prevention and treatment of NAFLD. The new mechanism of "Shenling Baizhu San" (SLBZS) is examined in this study for the prevention and treatment of NAFLD at the preclinical level.
Male C57BL/6J mice were randomly divided into three groups: normal diet (ND), western diet + CCl
injection (WDC), and SLBZS intervention (WDC + SLBZS). Body weights, energy intake, liver enzymes, pro-inflammatory factors, and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A, and HTR2B were tested using qRT-PCR or ELISA. Dynamic changes in the gut microbiota and metabolites were further detected through the 16S rRNA gene and untargeted metabolomics.
SLBZS intervention for 6 weeks could reduce the serum and liver lipid profiles, glucose, and pro-inflammatory factors while improving insulin resistance and liver function indexes in the mice, thus alleviating NAFLD in mice. More importantly, significant changes were found in the intestinal TPH-1, 5-HT, liver 5-HT, and related receptors HTR2A and HTR2B. The 16S rRNA gene analysis suggested that SLBZS was able to modulate the disturbance of gut microbiota, remarkably increasing the relative abundance of probiotics (
and
) and inhibiting the growth of pro-inflammatory bacteria (
and
) in mice with NAFLD. Combined with metabolomics in positive- and negative-ion-mode analyses, approximately 50 common differential metabolites were selected via non-targeted metabolomics detection, which indicated that the targeting effect of SLBZS included lipid metabolites, bile acids (BAs), amino acids (AAs), and tryptophan metabolites. In particular, the lipid metabolites 15-OxEDE, vitamin D3, desoxycortone, and oleoyl ethanol amide were restored by SLBZS.
Integrating the above results of multiple omics suggests that SLBZS ameliorates NAFLD via specific gut microbiota, gut-derived 5-HT, and related metabolites to decrease fat accumulation in the liver and inflammatory responses.
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