ABSTRACT
Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.
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OBJECTIVE: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center. METHODS: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7-297.6) months. RESULTS: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5-141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm3) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708-6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032-12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found. CONCLUSION: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism after a single GKRS.
Subject(s)
Adenoma , Hypopituitarism , Pituitary Neoplasms , Radiosurgery , Humans , Hypopituitarism/etiology , Hypopituitarism/epidemiology , Radiosurgery/adverse effects , Male , Female , Middle Aged , Pituitary Neoplasms/surgery , Adenoma/surgery , Adenoma/pathology , Adult , Retrospective Studies , Aged , Risk Factors , Follow-Up Studies , Young Adult , Adolescent , Incidence , Aged, 80 and over , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Treatment OutcomeABSTRACT
Space particle radiation is a major environmental factor in spaceflight, and it is known to cause body damage and even trigger cancer, but with unknown molecular etiologies. To examine these causes, we developed a systems biology approach by focusing on the co-expression network analysis of transcriptomics profiles obtained from single high-dose (SE) and multiple low-dose (ME) α-particle radiation exposures of BEAS-2B human bronchial epithelial cells. First, the differential network and pathway analysis based on the global network and the core modules showed that genes in the ME group had higher enrichment for the extracellular matrix (ECM)-receptor interaction pathway. Then, collagen gene COL1A1 was screened as an important gene in the ME group assessed by network parameters and an expression study of lung adenocarcinoma samples. COL1A1 was found to promote the emergence of the neoplastic characteristics of BEAS-2B cells by both in vitro experimental analyses and in vivo immunohistochemical staining. These findings suggested that the degree of malignant transformation of cells in the ME group was greater than that of the SE, which may be caused by the dysregulation of the ECM-receptor pathway.
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Deoxynivalenol (DON) has drawn considerable attention for its obvious pathogenicity and wide use in agro-products, which cause a potential threat to human health. In this work, an electrochemical immunosensor is developed for the highly sensitive and selective detection of DON in wheat flour using AuNPs-BP-MWCNTs-COOH and antibodies. The AuNPs-BP-MWCNTs-COOH nanocomposite was prepared via an in situ reduction reaction and ultrasonic-assisted liquid-phase exfoliation. The nanocomposite exhibits a larger surface area, decent stability, excellent electron transfer capability, good protein binding capability and prominent specificity. The plentiful carboxyl group on the nanocomposite can bind to the amino group of the antibody, and AuNPs have an affinity for the sulfhydryl group of the antibody, which makes it feasible for the nanocomposite to load the antibody. The peak currents are plotted against the logarithm of DON concentration from 0.002 to 80 ng mL-1 with a limit of detection (LOD) of 0.5 pg mL-1. This approach establishes an effective label-free immunosensor platform for the detection of DON with high sensitivity and selectivity in various food and agricultural products.
Subject(s)
Electrochemical Techniques , Flour , Gold , Metal Nanoparticles , Trichothecenes , Triticum , Trichothecenes/analysis , Trichothecenes/immunology , Flour/analysis , Triticum/chemistry , Metal Nanoparticles/chemistry , Gold/chemistry , Electrochemical Techniques/methods , Immunoassay/methods , Biosensing Techniques/methods , Limit of Detection , Nanotubes, Carbon/chemistry , Food Contamination/analysis , Nanocomposites/chemistryABSTRACT
BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy. Novel therapeutic modalities like tumor electric field therapy (TEFT) have shown promise, but underlying mechanisms remain unclear. The extracellular matrix (ECM) is implicated in GBM progression, warranting investigation into TEFT-ECM interplay. METHODS: T98G cells were treated with TEFT (200 kHz, 2.2 V/m) for 72 h. Collagen type VI alpha 1 (COL6A1) was identified as hub gene via comprehensive bioinformatic analysis based on RNA sequencing (RNA-seq) and public glioma datasets. TEFT intervention models were established using T98G and Ln229 cell lines. Pre-TEFT and post-TEFT GBM tissues were collected for further validation. Focal adhesion pathway activity was assessed by western blot. Functional partners of COL6A1 were identified and validated by co-localization and survival analysis. RESULTS: TEFT altered ECM-related gene expression in T98G cells, including the hub gene COL6A1. COL6A1 was upregulated in GBM and associated with poor prognosis. Muti-database GBM single-cell analysis revealed high-COL6A1 expression predominantly in malignant cell subpopulations. Differential expression and functional enrichment analyses suggested COL6A1 might be involved in ECM organization and focal adhesion. Western blot (WB), immunofluorescence (IF), and co-immunoprecipitation (Co-IP) experiments revealed that TEFT significantly inhibited expression of COL6A1, hindering its interaction with ITGA5, consequently suppressing the FAK/Paxillin/AKT pathway activity. These results suggested that TEFT might exert its antitumor effects by downregulating COL6A1 and thereby inhibiting the activity of the focal adhesion pathway. CONCLUSION: TEFT could remodel the ECM of GBM cells by downregulating COL6A1 expression and inhibiting focal adhesion pathway. COL6A1 could interact with ITGA5 and activate the focal adhesion pathway, suggesting that it might be a potential therapeutic target mediating the antitumor effects of TEFT.
Subject(s)
Brain Neoplasms , Collagen Type VI , Electric Stimulation Therapy , Glioblastoma , Collagen Type VI/genetics , Collagen Type VI/metabolism , Humans , Glioblastoma/genetics , Glioblastoma/therapy , Glioblastoma/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/therapy , Brain Neoplasms/pathology , Electric Stimulation Therapy/methods , Cell Line, Tumor , Animals , Mice, Nude , MiceABSTRACT
OBJECTIVE: To assess renal interstitial fibrosis (IF) using diffusion MRI approaches, and explore whether corticomedullary difference (CMD) of diffusion parameters, combination among MRI parameters, or combination with estimated glomerular filtration rate (eGFR) benefit IF evaluation. METHODS: Forty-two patients with chronic kidney disease were included, undergoing MRI examinations. MRI parameters from apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), and diffusion-relaxation correlated spectrum imaging (DR-CSI) were obtained both for renal cortex and medulla. CMD of these parameters was calculated. Pathological IF scores (1-3) were obtained by biopsy. Patients were divided into mild (IF = 1, n = 23) and moderate-severe fibrosis (IF = 2-3, n = 19) groups. Group comparisons for MRI parameters were performed. Diagnostic performances were assessed by the receiver operator's curve analysis for discriminating mild from moderate-severe IF patients. RESULTS: Significant inter-group differences existed for cortical ADC, IVIM-D, IVIM-f, DKI-MD, DR-CSI VB, and DR-CSI VC. Significant inter-group differences existed in ΔADC, ΔMD, ΔVB, ΔVC, ΔQB, and ΔQC. Among the cortical MRI parameters, VB displayed the highest AUC = 0.849, while ADC, f, and MD also showed AUC > 0.8. After combining cortical value and CMD, the diagnostic performances of the MRI parameters were slightly improved except for IVIM-D. Combining VB with f brings the best performance (AUC = 0.903) among MRI bi-variant models. A combination of cortical VB, ΔADC, and eGFR brought obvious improvement in diagnostic performance (AUC 0.963 vs 0.879, specificity 0.826 vs 0.896, and sensitivity 1.000 vs 0.842) than eGFR alone. CONCLUSION: Our study shows promising results for the assessment of renal IF using diffusion MRI approaches. CRITICAL RELEVANCE STATEMENT: Our study explores the non-invasive assessment of renal IF, an independent and effective predictor of renal outcomes, by comparing and combining diffusion MRI approaches including compartmental, non-compartmental, and model-free approaches. KEY POINTS: Significant difference exists for diffusion parameters between mild and moderate-severe IF. Generally, cortical parameters show better performance than corresponding CMD. Bi-variant model lifts the diagnostic performance for assessing IF.
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Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The Clinical Proteomic Tumor Analysis Consortium database, enriched with comprehensive cancer proteomics data including phosphorylation and ubiquitination profiles, alongside transcriptomics data from the Genomic Data Commons, allow for integrative molecular studies of cancer. The ProteoCancer Analysis Suite (PCAS), our newly developed R package and Shinyapp, leverages these resources to facilitate in-depth analyses of proteomics, phosphoproteomics, and transcriptomics, enhancing our understanding of the tumor microenvironment through features like immune infiltration and drug sensitivity analysis. This tool aids in identifying critical signaling pathways and therapeutic targets, particularly through its detailed phosphoproteomic analysis. To demonstrate the functionality of the PCAS, we conducted an analysis of GAPDH across multiple cancer types, revealing a significant upregulation of protein levels, which is consistent with its important biological and clinical significance in tumors, as indicated in our prior research. Further experiments were used to validate the findings performed using the tool. In conclusion, the PCAS is a powerful and valuable tool for conducting comprehensive proteomic analyses, significantly enhancing our ability to uncover oncogenic mechanisms and identify potential therapeutic targets in cancer research.
Subject(s)
Neoplasms , Proteomics , Humans , Proteomics/methods , Neoplasms/metabolism , Neoplasms/genetics , Tumor Microenvironment/genetics , Software , Computational Biology/methods , Proteome/metabolismABSTRACT
Broussonetia papyrifera is widely found in cadmium (Cd) contaminated areas, with an inherent enhanced flavonoids metabolism and inhibited lignin biosynthesis, colonized by lots of symbiotic fungi, such as arbuscular mycorrhizal fungi (AMF). However, the physiological and molecular mechanisms by which Rhizophagus irregularis, an AM fungus, regulates flavonoids and lignin in B. papyrifera under Cd stress remain unclear. Here, a pot experiment of B. papyrifera inoculated and non-inoculated with R. irregularis under Cd stress was carried out. We determined flavonoids and lignin concentrations in B. papyrifera roots by LC-MS and GC-MS, respectively, and measured the transcriptional levels of flavonoids- or lignin-related genes in B. papyrifera roots, aiming to ascertain the key components of flavonoids or lignin, and key genes regulated by R. irregularis in response to Cd stress. Without R. irregularis, the concentrations of eriodictyol, quercetin and myricetin were significantly increased under Cd stress. The concentrations of eriodictyol and genistein were significantly increased by R. irregularis, while the concentration of rutin was significantly decreased. Total lignin and lignin monomer had no alteration under Cd stress or with R. irregularis inoculation. As for flavonoids- or lignin-related genes, 26 genes were co-regulated by Cd stress and R. irregularis. Among these genes, BpC4H2, BpCHS8 and BpCHI5 were strongly positively associated with eriodictyol, indicating that these three genes participate in eriodictyol biosynthesis and were involved in R. irregularis assisting B. papyrifera to cope with Cd stress. This lays a foundation for further research revealing molecular mechanisms by which R. irregularis regulates flavonoids synthesis to enhance tolerance of B. papyrifera to Cd stress.
Subject(s)
Cadmium , Flavonoids , Plant Roots , Flavonoids/metabolism , Cadmium/metabolism , Plant Roots/microbiology , Plant Roots/metabolism , Lignin/metabolism , Morus/microbiology , Morus/metabolism , Morus/genetics , Stress, Physiological , Broussonetia/metabolism , Broussonetia/microbiology , Broussonetia/genetics , Mycorrhizae/physiology , Glomeromycota/physiology , Gene Expression Regulation, Plant , Soil Pollutants/metabolism , FungiABSTRACT
A heterostructured crystalline bilayer specimen is known to produce moiré fringes (MFs) in the conventional transmission electron microscopy (TEM). However, the understanding of how these patterns form in scanning transmission electron microscopy (STEM) remains limited. Here, we extended the double-scattering model to establish the imaging theory of MFs in STEM for a bilayer sample and applied this theory to successfully explain both experimental and simulated STEM images of a perovskite PbZrO3/SrTiO3 system. Our findings demonstrated that the wave vectors of electrons exiting from Layer-1 and their relative positions with the atomic columns of Layer-2 should be taken into account. The atomic column misalignment leads to a faster reduction in the intensity of the secondary scattering beam compared to the single scattering beam as the scattering angle increases. Consequently, the intensity distribution of MFs in the bright field (BF)-STEM can be still described as the product of two single atomic images. However, in high angle annular dark field (HAADF)-STEM, it is approximately described as the superposition of the two images. Our work not only fills a knowledge gap of MFs in incoherent imaging, but also emphasizes the importance of the coherent scattering restricted by the real space when analyzing the HAADF-STEM imaging.
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Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as â¼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.
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Neuroinflammation mediated by microglia plays an important role in the etiology of Parkinson's disease (PD). Rho family GTPase 3 (RND3) exerts anti-inflammatory effects and may act as a potential new inducer of neuroprotective phenotypes in microglia. However, whether RND3 can be used to regulate microglia activation or reduce neuroinflammation in PD remains elusive. The study investigated the microglia modulating effects and potential anti-inflammatory effects of RND3 in vivo and in vitro, using animal models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and cell models of BV-2 cells stimulated by LPS plus IFN-γ with or without RND3-overexpression. The results showed that RND3 was highly expressed in the MPTP-induced PD mouse model and BV-2 cells treated with LPS and IFN-γ. In vivo experiments confirmed that RND3 overexpression could modulate microglia phenotype and ameliorate MPTP-induced neuroinflammation through inhibiting activation of the NLRP3 inflammasome in substantia nigra pars compacta (SNpc). In vitro study showed that RND3 overexpression could attenuate the production of pro-inflammatory factors in BV2 cells stimulated by LPS and IFN-γ. Mechanistically, RND3 reduced the activation of the NLRP3 inflammasome upon LPS and IFN-γ stimulation. Taken together, these findings suggest that RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation.
Subject(s)
Inflammasomes , Mice, Inbred C57BL , Microglia , NLR Family, Pyrin Domain-Containing 3 Protein , Parkinson Disease , rho GTP-Binding Proteins , Animals , Microglia/metabolism , Microglia/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Mice , Inflammasomes/metabolism , Male , rho GTP-Binding Proteins/metabolism , rho GTP-Binding Proteins/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathology , Parkinson Disease/genetics , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/pathology , Lipopolysaccharides/pharmacology , Disease Models, Animal , Cell Polarity , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Interferon-gamma/metabolismABSTRACT
This study aims to investigate effects of arbuscular mycorrhizal fungi (AMF) inoculation on nitrogen (N) uptake and assimilation in Populus cathayana under drought stress (DS). Herein, we measured photosynthetic performance, antioxidant enzyme system, N level and N assimilation enzymes, proteins content and distribution, transcripts of genes associated with N uptake or transport in P. cathayana with AMF (AM) or without AMF (NM) under soil water limitation and adequate irrigation. Compared with NM-DS P. cathayana, the growth, gas exchange properties, antioxidant enzyme activities, total N content and the proportion of water-soluble and membrane-bound proteins in AM-DS P. cathayana were increased. Meanwhile, nitrate reductase (NR) activity, NO3- and NO2- concentrations in AM-DS P. cathayana were reduced, while NH4+ concentration, glutamine synthetase (GS) and glutamate synthetase (GOGAT) activities were elevated, indicating that AM symbiosis reduces NO3- assimilation while promoting NH4+ assimilation. Furthermore, the transcriptional levels of NH4+ transporter genes (PcAMT1-4 and PcAMT2-1) and NO3- transporter genes (PcNRT2-1 and PcNRT3-1) in AM-DS P. cathayana roots were significantly down-regulated, as well as NH4+ transporter genes (PcAMT1-6 and PcAMT4-3) in leaves. In AM P. cathayana roots, DS significantly up-regulated the transcriptional levels of RiCPSI and RiURE, the key N transport regulatory genes in AMF compared with adequate irrigation. These results indicated that AM N transport pathway play an essential role on N uptake and utilization in AM P. cathayana to cope with DS. Therefore, this research offers a novel perspective on how AM symbiosis enhances plant resilience to drought at aspect of N acquisition and assimilation.
Subject(s)
Droughts , Mycorrhizae , Nitrogen , Populus , Symbiosis , Populus/microbiology , Populus/metabolism , Populus/genetics , Populus/physiology , Mycorrhizae/physiology , Mycorrhizae/metabolism , Nitrogen/metabolism , Symbiosis/physiology , Gene Expression Regulation, Plant , Plant Proteins/metabolism , Plant Proteins/genetics , Plant Roots/microbiology , Plant Roots/metabolism , Photosynthesis/physiology , Drought ResistanceABSTRACT
PURPOSE: To study the capability of diffusion-relaxation correlation spectroscopic imaging (DR-CSI) on subtype classification and grade differentiation for small renal cell carcinoma (RCC). Histogram analysis for apparent diffusion coefficient (ADC) was studied for comparison. MATERIALS AND METHODS: A total of 61 patients with small RCC (< 4 cm) were included in the retrospective study. MRI data were reviewed, including a multi-b (0-1500 s/mm2) multi-TE (51-200 ms) diffusion weighted imaging (DWI) sequence. Region of interest (ROI) was delineated manually on DWI to include solid tumor. For each patient, a D-T2 spectrum was fitted and segmented into 5 compartments, and the volume fractions VA, VB, VC, VD, VE were obtained. ADC mapping was calculated, and histogram parameters ADC 90th, 10th, median, standard deviation, skewness and kurtosis were obtained. All MRI metrices were compared between clear cell RCC (ccRCC) and non-ccRCC group, and between high-grade and low-grade group. Receiver operator curve analysis was used to assess the corresponding diagnostic performance. RESULTS: Significantly higher ADC 90th, ADC 10th and ADC median, and significantly lower DR-CSI VB was found for ccRCC compared to non-ccRCC. Significantly lower ADC 90th, ADC median and significantly higher VB was found for high-grade RCC compared to low-grade. For identifying ccRCC from non-ccRCC, VB showed the highest area under curve (AUC, 0.861) and specificity (0.882). For differentiating high- from low-grade, ADC 90th showed the highest AUC (0.726) and specificity (0.786), while VB also displayed a moderate AUC (0.715). CONCLUSION: DR-CSI may offer improved accuracy in subtype identification for small RCC, while do not show better performance for small RCC grading compared to ADC histogram.
Subject(s)
Carcinoma, Renal Cell , Diffusion Magnetic Resonance Imaging , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/diagnostic imaging , Male , Female , Diffusion Magnetic Resonance Imaging/methods , Retrospective Studies , Middle Aged , Aged , Adult , Neoplasm Grading , Aged, 80 and over , Sensitivity and SpecificityABSTRACT
Analyzing the important nodes of complex systems by complex network theory can effectively solve the scientific bottlenecks in various aspects of these systems, and how to excavate important nodes has become a hot topic in complex network research. This paper proposes an algorithm for excavating important nodes based on the heat conduction model (HCM), which measures the importance of nodes by their output capacity. The number and importance of a node's neighbors are first used to determine its own capacity, its output capacity is then calculated based on the HCM while considering the network density, distance between nodes, and degree density of other nodes. The importance of the node is finally measured by the magnitude of the output capacity. The similarity experiments of node importance, sorting and comparison experiments of important nodes, and capability experiments of multi-node infection are conducted in nine real networks using the Susceptible-Infected-Removed model as the evaluation criteria. Further, capability experiments of multi-node infection are conducted using the Independent cascade model. The effectiveness of the HCM is demonstrated through a comparison with eight other algorithms for excavating important nodes.
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PURPOSE: Transforming growth factor (TGF-ß) plays a dual role in tumor progression as well as a pivotal role in radiation response. TGF-ß-related epigenetic regulations, including DNA methylation, histone modifications (including methylation, acetylation, phosphorylation, ubiquitination), chromatin remodeling and non-coding RNA regulation, have been found to affect the occurrence and development of tumors as well as their radiation response in multiple dimensions. Due to the significance of radiotherapy in tumor treatment and the essential roles of TGF-ß signaling in radiation response, it is important to better understand the role of epigenetic regulation mechanisms mediated by TGF-ß signaling pathways in radiation-induced targeted and non-targeted effects. CONCLUSIONS: By revealing the epigenetic mechanism related to TGF-ß-mediated radiation response, summarizing the existing relevant adjuvant strategies for radiotherapy based on TGF-ß signaling, and discovering potential therapeutic targets, we hope to provide a new perspective for improving clinical treatment.
Subject(s)
Epigenesis, Genetic , Signal Transduction , Transforming Growth Factor beta , Transforming Growth Factor beta/metabolism , Humans , Epigenesis, Genetic/radiation effects , Signal Transduction/radiation effects , Animals , Neoplasms/radiotherapy , Neoplasms/genetics , Neoplasms/metabolism , DNA Methylation/radiation effects , Radiation ToleranceABSTRACT
Parkinson's disease (PD) is a gradually debilitating neurodegenerative syndrome. Here, we analyzed GSE7621 chip data obtained from the Gene Expression Omnibus (GEO) database to explore the pathogenesis of PD. Early B Cell Factor 3 (EBF3), a member of the highly evolutionarily conserved EBF-transcription factor family, is involved in neuronal development. EBF3 expression is low in the substantia nigra of patients with PD. However, whether EBF3 is implicated in dopaminergic neuron death during PD has not yet been investigated. Therefore, we aimed to reveal the potential anti-apoptotic effect and molecular mechanism of EBF3 in PD. We established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model in vivo and a 1-methyl-4-phenylpyridine (MPP+)-induced SH-SY5Y cell model in vitro. EBF3 was downregulated in the substantia nigra of PD mice and SH-SY5Y cells treated with MPP+, and the m6A methylation modification level was low. Fat mass and obesity-associated protein (FTO) siRNA upregulated m6A methylation modification of EBF3 and extended the EBF3 mRNA half-life. Functionally, as demonstrated by the results of the open-field test, pole test and gait analysis, EBF3 overexpression ameliorated MPTP-induced behavioral disorder. Further, EBF3 overexpression suppressed neuronal apoptosis in vivo, as evidenced by decreased TUNEL+ cells, and the increased activation of caspase-3 and caspase-9. Similar results were obtained in vitro, as reflected by increased cell viability, decreased LDH activity and restored mitochondrial function, collectively protecting SH-SY5Y cells from MPP+-induced apoptosis. Mechanistically, the results of luciferase reporter, ch-IP and DNA pull-down assays confirmed that, as a transcription factor, EBF3 bound to the promoter of CNTNAP4 (a protein associated with neuronal differentiation) and directly regulated CNTNAP4 transcription. Strikingly, CNTNAP4 knockdown markedly abolished the effect of EBF3 on cell apoptosis, thus aggravating PD. In conclusion, the low level of m6A methylation modification may contribute to the low expression of EBF3 during PD. Additionally, EBF3 attenuates PD by activating CNTNAP4 transcription, suggesting that EBF3 may be a novel therapeutic target in PD.
Subject(s)
Neuroblastoma , Parkinson Disease , Animals , Humans , Mice , Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Apoptosis , Cell Line, Tumor , Contactins/metabolism , Dopaminergic Neurons/metabolism , Mice, Inbred C57BL , Neuroblastoma/metabolism , Parkinson Disease/metabolism , Transcription Factors/metabolismABSTRACT
In terrestrial ecosystems, most plant species can form beneficial associations with arbuscular mycorrhizal (AM) fungi. Arbuscular mycorrhizal fungi benefit plant nutrient acquisition and enhance plant tolerance to drought. The high osmolarity glycerol 1 mitogen-activated protein kinase (HOG1-MAPK) cascade genes have been characterized in Rhizophagus irregularis. However, the upstream receptor of the HOG1-MAPK cascade remains to be investigated. We identify the receptor kinase RiSho1 from R. irregularis, containing four transmembrane domains and one Src homology 3 (SH3) domain, corresponding to the homologue of Saccharomyces cerevisiae. Higher expression levels of RiSho1 were detected during the in planta phase in response to drought. RiSho1 protein was localized in the plasma membrane of yeast, and interacted with the HOG1-MAPK module RiPbs2 directly by protein-protein interaction. RiSho1 complemented the growth defect of the yeast mutant ∆sho1 under sorbitol conditions. Knock-down of RiSho1 led to the decreased expression of downstream HOG1-MAPK cascade (RiSte11, RiPbs2, RiHog1) and drought-resistant genes (RiAQPs, RiTPSs, RiNTH1 and Ri14-3-3), hampered arbuscule development and decreased plants antioxidation ability under drought stress. Our study reveals the role of RiSho1 in regulating arbuscule development and drought-resistant genes via the HOG1-MAPK cascade. These findings provide new perspectives on the mechanisms by which AM fungi respond to drought.
Subject(s)
Droughts , Mycorrhizae , Symbiosis , Mycorrhizae/physiology , Symbiosis/genetics , Symbiosis/physiology , Adaptation, Physiological/genetics , Fungal Proteins/metabolism , Fungal Proteins/genetics , Saccharomyces cerevisiae/genetics , Gene Expression Regulation, Plant , Medicago truncatula/microbiology , Medicago truncatula/genetics , Medicago truncatula/enzymology , Drought Resistance , FungiABSTRACT
A substantial ferroelectric polarization is the key for designing high-performance ferroelectric nonvolatile memories. As a promising candidate system, the BaTiO3/La0.67Sr0.33MnO3 (BTO/LSMO) ferroelectric/ferromagnetic heterostructure has attracted a lot of attention thanks to the merits of high Curie temperature, large spin polarization, and low ferroelectric coercivity. Nevertheless, the BTO/LSMO heterostructure suffers from a moderate FE polarization, primarily due to the quick film-thickness-driven strain relaxation. In response to this challenge, we propose an approach for enhancing the FE properties of BTO films by using a Sr3Al2O6 (SAO) buffering layer to mitigate the interfacial strain relaxation. The continuously tunable strain allows us to illustrate the linear dependence of polarization on epitaxial strain with a large strain-sensitive coefficient of â¼27 µC/cm2 per percent strain. This results in a giant polarization of â¼80 µC/cm2 on the BTO/LSMO interface. Leveraging this large polarization, we achieved a giant tunneling electroresistance (TER) of â¼105 in SAO-buffered Pt/BTO/LSMO ferroelectric tunnel junctions (FTJs). Our research uncovers the fundamental interplay between strain, polarization magnitude, and device performance, such as on/off ratio, thereby advancing the potential of FTJs for next-generation information storage applications.
ABSTRACT
The remediation of heavy metals/metalloids (HMs) co-contaminated soil by solid wastes-based stabilizers (SWBS) has received major concern recently. Based on the literature reported in the latest years (2010-2023), this review systematically summarizes the different types of solid wastes (e.g., steel slag, coal fly ash, red mud, and sewage sludge, etc.) employed to stabilize HMs contaminated soil, and presents results from laboratory and field experiments. Firstly, the suitable solid wastes for soil remediation are reviewed, and the pros and cons are presented. Thereafter, the technical feasibility and economic benefit are evaluated for field application. Moreover, evaluation methods for remediation of different types of HMs-contaminated soil and the effects of SWBS on soil properties are summarized. Finally, due to the large specific surface, porous structure, and high reactivity, the SWBS can effectively stabilize HMs via adsorption, complexation, co/precipitation, ion exchange, electrostatic interaction, redox, and hydration process. Importantly, the environmental implications and long-term effectiveness associated with the utilization of solid wastes are highlighted, which are challenges for practical implementation of soil stabilization using SWBS, because the aging of soil/solid wastes has not been thoroughly investigated. Future attention should focus on modifying the SWBS and establishing an integrated long-term stability evaluation method.