Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal ...cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.
Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and ...intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas.
IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms.
The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%*), dentate gyrus (27.3, 75.0%*), and subventricular zone (4.5, 57.8%*). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3*, 100.0%*; middle cerebral arteries, 25.9%*, 100%*; anterior communicating arteries, 30.8*, 41.7%*; and carotid arteries, 51.5*, 77.6*). Relative reduction of integral dose to the infratentorial brain (190.7*, 109.7%*), supratentorial brain without PTV (9.6, 26.8%*), brainstem (45.6, 22.4%*), and whole brain without PTV (19.4*, 34.4%*) were recorded with the use of proton therapy. (*Differences were significant based on Friedman's test with Bonferroni-Dunn correction, α = 0.05)
The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.
Multilocus variation—pathogenic variants in two or more disease genes—can potentially explain the underlying genetic basis for apparent phenotypic expansion in cases for which the observed clinical ...features extend beyond those reported in association with a “known” disease gene.
Analyses focused on 106 patients, 19 for whom apparent phenotypic expansion was previously attributed to variation at known disease genes. We performed a retrospective computational reanalysis of whole-exome sequencing data using stringent Variant Call File filtering criteria to determine whether molecular diagnoses involving additional disease loci might explain the observed expanded phenotypes.
Multilocus variation was identified in 31.6% (6/19) of families with phenotypic expansion and 2.3% (2/87) without phenotypic expansion. Intrafamilial clinical variability within two families was explained by multilocus variation identified in the more severely affected sibling.
Our findings underscore the role of multiple rare variants at different loci in the etiology of genetically and clinically heterogeneous cohorts. Intrafamilial phenotypic and genotypic variability allowed a dissection of genotype–phenotype relationships in two families. Our data emphasize the critical role of the clinician in diagnostic genomic analyses and demonstrate that apparent phenotypic expansion may represent blended phenotypes resulting from pathogenic variation at more than one locus.
Although the genome of Chinese white pear ('Dangshansuli') has been released, little is known about the functions, evolutionary history and expression patterns of NAC families in this species to ...date.
In this study, we identified a total of 183 NAC transcription factors (TFs) in the pear genome, among which 146 pear NAC (PbNAC) members were mapped onto 16 chromosomes, and 37 PbNAC genes were located on scaffold contigs. No PbNAC genes were mapped to chromosome 2. Based on gene structure, protein motif analysis, and topology of the phylogenetic tree, the pear PbNAC family was classified into 33 groups. By comparing and analyzing the unique NAC subgroups in Rosaceae, we identified 19 NAC subgroups specific to pear. We also found that whole-genome duplication (WGD)/segmental duplication played critical roles in the expansion of the NAC family in pear, such as the 83 PbNAC duplicated gene pairs dated back to the two WGD events. Further, we found that purifying selection was the primary force driving the evolution of PbNAC family genes. Next, we used transcriptomic data to study responses to drought and cold stresses in pear, and we found that genes in groups C2f, C72b, and C100a were related to drought and cold stress response.
Through the phylogenetic, evolutionary, and expression analyses of the NAC gene family in Chinese white pear, we indentified 11 PbNAC TFs associated with abiotic stress in pear.
The optical microscope is customarily an instrument of substantial size and expense but limited performance. Here we report an integrated microscope that achieves optical performance beyond a ...commercial microscope with a 5×, NA 0.1 objective but only at 0.15 cm
and 0.5 g, whose size is five orders of magnitude smaller than that of a conventional microscope. To achieve this, a progressive optimization pipeline is proposed which systematically optimizes both aspherical lenses and diffractive optical elements with over 30 times memory reduction compared to the end-to-end optimization. By designing a simulation-supervision deep neural network for spatially varying deconvolution during optical design, we accomplish over 10 times improvement in the depth-of-field compared to traditional microscopes with great generalization in a wide variety of samples. To show the unique advantages, the integrated microscope is equipped in a cell phone without any accessories for the application of portable diagnostics. We believe our method provides a new framework for the design of miniaturized high-performance imaging systems by integrating aspherical optics, computational optics, and deep learning.
In this letter, we present a new generalized cyclotomic method over Z 3p based on the Chinese remainder theorem and the cyclotomic classes of order 2. Two new families of binary sequence pairs of ...period N = 3p with optimal three-level correlation values are constructed by utilizing these new generalized cyclotomic classes, where p > 3 is an odd prime. All the constructed binary sequence pairs have optimal correlation values {-3, 1} or {-1, 3}.
•Study on sandwich composites considering the in-service load and lay-ups of wind turbine blades for the first time.•Reveal the effect of foam core density on in-plane compressive strength and ...failure behaviors of sandwich composites.•Reveal the effect of core machining configuration on in-plane compressive strength and failure behaviors of sandwich composites.•Provide a basis for the failure analysis of wind turbine blades in wind farms from the failure modes of sandwich composites found in this paper.
Composite sandwich structure, as the largest part of wind turbine blades, often experiences complex failure phenomena during full-scale blade testing and wind farm operation. In order to better understand failure behaviors and reveal the failure mechanism of sandwich structures for wind turbine blades, composite sandwich samples were designed, fabricated, and tested in consideration of the real laminate and core machining configuration, manufacturing process, and dominating load of wind turbine blades, In-plane compressive strength and failure behaviors were investigated by experimental and theoretic methods. It was found that the grooved with perforations and cut (GPC) machining configuration can improve in-plane compressive strength of sandwich samples more than that of the double grooved with perforations (DGP) configuration due to higher core shear modulus, the failure mode of sandwich samples shifted from global buckling for Plain configuration to a combination of core shearing and skin/core debonding at both sides for DGP configuration, and finally to skin/core debonding at the shallow groove core side for GPC configuration. The failure mode of sandwich samples with DGP core mainly transferred from global buckling to a combination of core shearing and skin/core debonding at both sides, and further to skin/core debonding at both sides alone with increasing foam density. All samples with GPC core exhibited skin/core debonding at the shallow groove side after slight buckling, which was driven by the asymmetric structure of the GPC core. Classical methods can reasonably predict failure loads of sandwich samples with Plain and DGP cores, but overestimate that of sandwich samples with GPC core.
Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with ...hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio OR = 26.98, p < .001) and JAK mutation (OR = 17.32, p = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis.
What is the context?
Platelet transfusion refractoriness is a critical issue, and it greatly increases bleeding risks and hospitalization costs.
Patients with hematological diseases tend to develop PTR.
PTR results from immune and nonimmune factors and the latter account for 80-90%.
At present, there are few studies focused on the inducing factors of PTR, and the specific mechanism is not clear.
What is new?
In this study, we investigated 108 patients with hematological disorders who received allogeneic HSCT from January 2019 to December 2020.
We found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases.
PTR had a passive effect on the prognosis of patients after HSCT, as indicated by worse OS and a trend toward lower platelets after transplantation.
PTR might affect megakaryocyte reconstitution after transplantation.
What is the impact?
This study provides evidence that hematological patients with splenomegaly should be alert to the occurrence of PTR, which often indicates a worse prognosis of transplantation.
Spleen reduction and JAK inhibitors in the treatment of PTR are worth exploring.
Abbreviations
PLT: platelets; PTR: platelet transfusion refractoriness; HSCT: hematopoietic stem cell transplantation; OR: odds ratio; HR: hazard ratio; CI: confidence interval; IQR: interquartile range; SD: standard deviation; HLA: human leukocyte antigen; HPA: human platelet antigen; OS: overall survival; RFS: relapse free survival; PI: post-transfusion increment; PPR: percentage platelet recovery; CCI: corrected count increment; ICU: intensive care unit; AA: aplastic anemia; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; ALL: acute lymphocytic leukemia; CML: chronic myeloid leukemia; CMML: chronic myelomonocytic leukemia; MPN: myeloproliferative neoplasm; SI: splenic irradiation; Abs: antibodies; CR: complete remission; DAC: decitabine; GVHD: graft-versus-host disease; BM: bone marrow; PB: peripheral blood
This study aims to explain the role and related mechanisms of long non-coding RNA (lncRNA) X inactive specific transcript (XIST) in sepsis-induced acute lung injury (ALI). The in vivo septic models ...and in vitro septic model were established. In animal models, the lung injury of the rats was evaluated after XIST was overexpressed. In cell models, the effects of XIST and microRNA (miR)-16-5p on ALI was detected by MTT assay, Western blot and ELISA. The interaction between XIST and miR-16-5p was investigated by bioinformatics analysis, dual-luciferase reporter assay, RIP assay and RNA pull-down assay. We found that XIST expression was down-regulated in lung tissues of septic rats and lipopolysaccharide-stimulated cells, while the expression of miR-16-5p was up-regulated. Down-regulation of XIST significantly promoted pulmonary edema, increased the levels of TNF-α, IL-1β and malondialdehyde, inhibited the cell viability and decreased the level of superoxide dismutase. Mechanistically, it was confirmed that XIST could sponge miR-16-5p, and thus repress its expression, and the transfection of miR-16-5p mimics could reverse the effects of XIST over-expression in the cell model. Collectively, it is concluded that XIST reduces sepsis-induced ALI via regulating miR-16-5p.
The
pathway genes play an essential role in shoot apical meristem maintenance and floral organ development, and under intense selection during crop domestication. The carpel number is an important ...fruit trait that affects fruit shape, size and internal quality in cucumber, but the molecular mechanism remains elusive. Here, we found that
expression was negatively correlated with carpel number in cucumber cultivars.
led to increased number of petals and carpels, whereas overexpression of
resulted in more sepals, petals and carpels, suggesting that
and
function as a negative and a positive regulator for carpel number variation, respectively. Biochemical analyses indicated that CsWUS directly bound to the promoter of
and activated its expression. Overexpression of
, a
-
MADS-box gene, resulted in more petals and carpels. CsFUL1
can directly bind to the
promoter to stimulate its expression. Furthermore, we found that auxin participated in carpel number variation in cucumber through interaction of CsARF14 with CsWUS. Therefore, we have identified a gene regulatory pathway involving
,
,
and
in determining carpel number variation in an important vegetable crop - cucumber.
PDF
