Abnormal expression of the eukaryotic initiation factor 3 (eIF3) subunits plays critical roles in tumorigenesis and progression, and also has potential prognostic value in cancers. However, the ...expression and clinical implications of eIF3 subunits in glioma remain unknown.
Expression data of eIF3 for patients with gliomas were obtained from the Chinese Glioma Genome Atlas (CGGA) (
= 272) and The Cancer Genome Atlas (TCGA) (
= 595). Cox regression, the receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to study the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were utilized for functional prediction.
In both the CGGA and TCGA datasets, the expression levels of eIF3d, eIF3e, eIF3f, eIF3h and eIF3l highly were associated with the IDH mutant status of gliomas. The expression of eIF3b, eIF3i, eIF3k and eIF3m was increased with the tumor grade, and was associated with poorer overall survival All Hazard ratio (HR) > 1 and P < 0.05. By contrast, the expression of eIF3a and eIF3l was decreased in higher grade gliomas and was associated with better overall survival (Both HR < 1 and P < 0.05). Importantly, the expression of eIF3i (located on chromosome 1p) and eIF3k (Located on chromosome 19q) were the two highest risk factors in both the CGGA eIF3i HR = 2.068 (1.425-3.000); eIF3k HR = 1.737 (1.166-2.588) and TCGA eIF3i HR = 1.841 (1.642-2.064); eIF3k HR = 1.521 (1.340-1.726) databases. Among eIF3i, eIF3k alone or in combination, the expression of eIF3i was the more robust in stratifying the survival of glioma in various pathological subgroups. The expression of eIF3i was an independent prognostic factor in IDH-mutant lower grade glioma (LGG) and could also predict the 1p/19q codeletion status of IDH-mutant LGG. Finally, GO and GSEA analysis showed that the elevated expression of eIF3i was significantly correlated with the biological processes of cell proliferation, mRNA processing, translation, T cell receptor signaling, NF-κB signaling and others.
Our study reveals the expression alterations during glioma progression, and highlights the prognostic value of eIF3i in IDH-mutant LGG.
The human riboflavin transporter-3 (encoded by
SLC52A3
) plays a prominent role in riboflavin absorption. Interestingly, abnormal expression patterns of SLC52A3 in multiple types of human cancers ...have been recently noted. However, the molecular mechanisms underlying its dysregulation remain unclear. In this study, we find that SLC52A3 has two transcript variants that differ in the transcriptional start site, and encode different proteins: SLC52A3a and SLC52A3b. Importantly, aberrant expressions of SLC52A3 are associated with stepwise development of esophageal squamous cell carcinoma (ESCC) as well as the survival rates of ESCC patients. Functionally, SLC52A3a, but not SLC52A3b, strongly promotes the proliferation and colony formation of ESCC cells. Furthermore,
SLC52A3
5′-flanking regions contain NF-κB p65/Rel-B-binding sites, which are crucial for mediating
SLC52A3
transcriptional activity in ESCC cells. Chromatin immunoprecipitation and electrophoretic mobility shift assay reveal that p65/Rel-B bind to 5′-flanking regions of
SLC52A3
. Accordingly, NF-κB signaling upregulates SLC52A3 transcription upon TNFα stimulation. Taken together, these results elucidate the mechanisms underlying SLC52A3 overexpression in ESCC. More importantly, our findings identify SLC52A3 as both a predictive and prognostic biomarker for this deadly cancer.
Objective
To determine the efficacy of CXCL5 administration in lupus‐prone MRL/lpr (Faslpr) mice and elucidate its working mechanisms.
Methods
CXCL5 expression in blood (obtained from SLE patients ...and Faslpr mice) and major internal organs (obtained from Faslpr mice) was examined by Luminex, real‐time polymerase chain reaction, and immunofluorescent staining analyses. Pharmacokinetic studies were performed in Faslpr mice and healthy Institute of Cancer Research mice. Efficacy of CXCL5 administration was demonstrated in Faslpr mice, and the working mechanism of CXCL5 treatment was elucidated by flow cytometry, Luminex, and RNA sequencing.
Results
In SLE patients, serum CXCL5 levels were significantly lower than in healthy individuals (P < 0.0001) and negatively correlated with disease activity (P = 0.004). In Faslpr mice, disease severity progressed with age and was negatively associated with plasma CXCL5 levels. Intravenous administration of CXCL5 to Faslpr mice restored endogenous circulatory CXCL5, improved mice survival, and reduced anti–double‐stranded DNA antibodies, proteinuria, lupus nephritis activity and chronicity indices, renal complements, and neutrophil extracellular traps over short‐term (10 weeks) and long‐term (2 years) time periods. In vitro and in vivo assays demonstrated that CXCL5 dictated neutrophil trafficking and suppressed neutrophil activation, degranulation, proliferation, and renal infiltration. Renal and splenic RNA sequencing further showed that CXCL5‐mediated immunomodulation occurred by promoting energy production in renal‐infiltrated immune cells, activating certain T cells, and reducing tissue fibrosis, granulocyte extravasation, complement components, and interferons. Further factorial design results indicated that CXCL5 appears to enhance host tolerability to cyclophosphamide in vulnerable individuals.
Conclusion
We found that serum CXCL5 levels were significantly lower in SLE patients than in healthy individuals and were negatively correlated with disease activity. By administering CXCL5 intravenously in a mouse model of lupus, mouse survival improved, and indices of disease activity reduced significantly. Taken together, these findings indicate CXCL5 administration may represent a novel myeloid/neutrophil‐targeting therapy for SLE.
Considering past studies on the orthotropic anisotropy of arteries in the circumferential and axial directions, this work aims to experimentally study the anisotropic behaviour of arteries by ...tensioning multi-directional strips of porcine thoracic aorta.
Histology is first analyzed by staining arterial sections of three orthotropic (axial, circumferential, and radial) planes. 168 stripped samples from 21 aortas are categorized into three loading-rate groups to investigate the influence of loading rates on the Young's modulus and ultimate stress. Basing on the Young's modulus and ultimate stress, the degree of anisotropy is calculated. Moreover, 24 stripped samples from 3 aortas are tested to study the relaxation anisotropy of arteries by fitting the experimental data with a five-parameter Maxwell reduced relaxation function.
Histological analysis shows the parallel orientation of crimpled collagen and elastin fibres. The Young's modulus and ultimate stress reach the greatest in the circumferential direction, and the smallest in the axial direction, respectively, and the values in the other directions are in-between; moreover, the two parameters monotonously increase as the samples orientate from the axial to circumferential directions. The Young's modulus is more sensitive to the loading rate than the ultimate stress. The degree of anisotropy calculated by the Young's modulus is similar to that by the ultimate stress, and it is independent of loading rates. Stress-relaxation also exhibits anisotropy, whose variation is consistent with those of the two parameters.
Due to the stress-growth rule, fibre preferably orientates in the circumferential direction, and the preferable orientation results in great mechanical parameters, anisotropy, and small relaxation behaviour of arteries. The work extends the studies on the arterial anisotropy instead of only the circumferential and axial directions, and could be useful to comprehensively understand the anisotropy of arteries.
The current research takes advantage of the low solubility and hepatoprotective activity of the phenolic acid nutrient vanillic acid (VAA) to reduce the solubility and dissolution rate of the ...antifungal drug 5-fluorocytosine (FCY)
via
a cocrystallization strategy, thus gaining new insights into surmounting the dose-limited hepatotoxicity caused by the rapid and almost complete absorption of FCY. An FCY-phenolic acid nutraceutical cocrystal, namely, FCY–VAA–H
2
O, was directionally self-assembled and structurally characterized. The single-crystal X-ray structural analysis showed that water and VAA molecules occupy the polar sites of FCY
in situ
through strong hydrogen-bonding interplays, establishing a key plane structure (KPS) with hydrophobicity, which down-regulates the solubility and dissolution rate of the cocrystal as compared with FCY itself. The conclusion is supported by systematic theoretical studies. Molecular electrostatic potential (MEP) calculations revealed a polarity decrease in KPS in the cocrystal relative to free FCY, in accordance with the polarity diminution induced by intensive hydrogen-bonding energy, through the reduced density gradient (RDG) analysis, implying an obvious potentiation in hydrophobicity. Thereby, the theoretical calculations achieved positive correlations with the experimental measurements.
The Normalized Difference Snow Index (NDSI) is an effective index for snow-cover mapping at large scales, but in forested regions the identification accuracy for snow using the NDSI is low because of ...forest cover effects. In this study, typical evergreen coniferous forest zones on Qilian Mountain in the Upper Heihe River Basin (UHRB) were chosen as example regions. By analyzing the spectral signature of snow-covered and snow-free evergreen coniferous forests with Landsat Operational Land Imager (OLI) data, a novel spectral band ratio using near-infrared (NIR) and shortwave infrared (SWIR) bands, defined as (ρnir − ρswir)/(ρnir + ρswir), is proposed. Our research shows that this band ratio, named the normalized difference forest snow index (NDFSI), can be used to effectively distinguish snow-covered evergreen coniferous forests from snow-free evergreen coniferous forests in UHRB.
Graphene oxide (GO) is a good candidate for high-performance humidity sensors with high responsitivity and rapid response. The GO sensoring mechanism is highly concerned and still not yet well ...understood. In this study, a systematic examination of GO capacitive humidity sensors was performed, revealing GO sensors’ excellent sensitivity properties with two orders of capacitance change (within a relative humidity range of 12–97 RH%) and sub-0.1 s (τ95) response at room temperature being observed. A Fourier transform infrared technique was used to study the structural characteristics of GO films under both steady and transient humidity states. Interaction of water molecules with the functional groups in GO was detected, which induced evident changes of the GO structure and directly related to the sensoring processes. Free-state liquid water was found to play an important role in the sensoring processes. A synergistic sensoring mechanism is suggested: functional groups work to reserve water and produce a larger layer space for better water transportation, while regions without functional groups work as effective channels for water transportation.
The applications of sulphate-reducing microorganisms (SRMs) in acid mine drainage (AMD) treatment systems have received extensive attention due to their ability to reduce sulphate and stabilize ...metal(loid)s. Despite great phylogenetic diversity of SRMs, only a few have been used in AMD treatment bioreactors. In situ enrichment could be an efficient approach to select new effective SRMs for AMD treatment. Here, we performed in situ enrichment of SRMs in highly stratified AMD sediment cores using different kinds of carbon source mixture. The dsrAB (dissimilatory sulfite reductase) genes affiliated with nine phyla (two archaeal and seven bacterial phyla) and 26 genera were enriched. Remarkably, those genes affiliated with Aciduliprofundum and Vulcanisaeta were enriched in situ in AMD-related environments for the first time, and their relative abundances were negatively correlated with pH. Furthermore, 107 dsrAB-containing metagenome-assembled genomes (MAGs) were recovered from metagenomic datasets, with 14 phyla (two archaeal and 12 bacterial phyla) and 15 genera. The relative abundances of MAGs were positively correlated with total carbon and sulphate contents. Our findings expanded the diversity of SRMs that can be enriched in AMD sediment, and revealed the physiochemical properties that might affect the growth of SRMs, which provided guidance for AMD treatment bioreators.
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•Successful in situ enrichment of SRMs in acid mine drainage sediment•Mixed carbon sources has a positive effect on SRMs enrichments.•Multiple parameters affect relative abundance of SRMs in situ.•Enrichments of more diverse SRMs could be used in AMD bioreactor.
Functionalization of porous titanium alloy implants with bioactive coatings to improve bone regeneration performance is hotly pursued in recent decade. Here we demonstrate a facile strategy to design ...bioactive 3D printed porous titanium implants with strontium (Sr) ion incorporated zeolite coatings (SZCs). The SZCs can be uniformly fabricated on the 3D porous scaffolds using an in situ hydrothermal crystal growth method to improve their osteogenesis and osteointegration capacity. In vitro experiments of SZCs on a TC4 disk show that Sr ions can slowly release in the simulated body fluid by means of ion-exchange, thus can drastically improve apatite forming ability, biocompatibility, corrosion resistance, and alkaline phosphatase (ALP) activity. In vivo evaluation on a rabbit model with 3D printed titanium implants shows that the SZCs could significantly induce new bone formation both in and around the porous implants within four weeks. This work may open up a new method for the development of bioactive customized porous implants by functionalization with zeolite coatings for orthopedic applications.
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