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Moiré superlattices formed by twisted stacking in van der Waals materials have emerged as a new platform for exploring the physics of strongly correlated materials and other emergent phenomena1-5. However, there remains a lack of research on the mechanical properties of twisted-layer van der Waals materials, owing to a lack of suitable strategies for making three-dimensional bulk materials. Here we report the successful synthesis of a polycrystalline boron nitride bulk ceramic with high room-temperature deformability and strength. This ceramic, synthesized from an onion-like boron nitride nanoprecursor with conventional spark plasma sintering and hot-pressing sintering, consists of interlocked laminated nanoplates in which parallel laminae are stacked with varying twist angles. The compressive strain of this bulk ceramic can reach 14% before fracture, about one order of magnitude higher compared with traditional ceramics (less than 1% in general), whereas the compressive strength is about six times that of ordinary hexagonal boron nitride layered ceramics. The exceptional mechanical properties are due to a combination of the elevated intrinsic deformability of the twisted layering in the nanoplates and the three-dimensional interlocked architecture that restricts deformation from propagating across individual nanoplates. The advent of this twisted-layer boron nitride bulk ceramic opens a gate to the fabrication of highly deformable bulk ceramics.
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Grain boundaries (GBs), with their diversity in both structure and structural transitions, play an essential role in tailoring the properties of polycrystalline materials1-5. As a unique GB subset, {112} incoherent twin boundaries (ITBs) are ubiquitous in nanotwinned, face-centred cubic materials6-9. Although multiple ITB configurations and transitions have been reported7,10, their transition mechanisms and impacts on mechanical properties remain largely unexplored, especially in regard to covalent materials. Here we report atomic observations of six ITB configurations and structural transitions in diamond at room temperature, showing a dislocation-mediated mechanism different from metallic systems11,12. The dominant ITBs are asymmetric and less mobile, contributing strongly to continuous hardening in nanotwinned diamond13. The potential driving forces of ITB activities are discussed. Our findings shed new light on GB behaviour in diamond and covalent materials, pointing to a new strategy for development of high-performance, nanotwinned materials.
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Understanding the direct transformation from graphite to diamond has been a long-standing challenge with great scientific and practical importance. Previously proposed transformation mechanisms1-3, based on traditional experimental observations that lacked atomistic resolution, cannot account for the complex nanostructures occurring at graphite-diamond interfaces during the transformation4,5. Here we report the identification of coherent graphite-diamond interfaces, which consist of four basic structural motifs, in partially transformed graphite samples recovered from static compression, using high-angle annular dark-field scanning transmission electron microscopy. These observations provide insight into possible pathways of the transformation. Theoretical calculations confirm that transformation through these coherent interfaces is energetically favoured compared with those through other paths previously proposed1-3. The graphite-to-diamond transformation is governed by the formation of nanoscale coherent interfaces (diamond nucleation), which, under static compression, advance to consume the remaining graphite (diamond growth). These results may also shed light on transformation mechanisms of other carbon materials and boron nitride under different synthetic conditions.
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The well known trade-off between hardness and toughness (resistance to fracture) makes simultaneous improvement of both properties challenging, especially in diamond. The hardness of diamond can be increased through nanostructuring strategies1,2, among which the formation of high-density nanoscale twins - crystalline regions related by symmetry - also toughens diamond2. In materials other than diamond, there are several other promising approaches to enhancing toughness in addition to nanotwinning3, such as bio-inspired laminated composite toughening4-7, transformation toughening8 and dual-phase toughening9, but there has been little research into such approaches in diamond. Here we report the structural characterization of a diamond composite hierarchically assembled with coherently interfaced diamond polytypes (different stacking sequences), interwoven nanotwins and interlocked nanograins. The architecture of the composite enhances toughness more than nanotwinning alone, without sacrificing hardness. Single-edge notched beam tests yield a toughness up to five times that of synthetic diamond10, even greater than that of magnesium alloys. When fracture occurs, a crack propagates through diamond nanotwins of the 3C (cubic) polytype along {111} planes, via a zigzag path. As the crack encounters regions of non-3C polytypes, its propagation is diffused into sinuous fractures, with local transformation into 3C diamond near the fracture surfaces. Both processes dissipate strain energy, thereby enhancing toughness. This work could prove useful in making superhard materials and engineering ceramics. By using structural architecture with synergetic effects of hardening and toughening, the trade-off between hardness and toughness may eventually be surmounted.
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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.
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Inflamasomas , Ratones Endogámicos C57BL , Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedad de Parkinson , Proteínas de Unión al GTP rho , Animales , Microglía/metabolismo , Microglía/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ratones , Inflamasomas/metabolismo , Masculino , Proteínas de Unión al GTP rho/metabolismo , Proteínas de Unión al GTP rho/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/genética , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Lipopolisacáridos/farmacología , Modelos Animales de Enfermedad , Polaridad Celular , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Inflamación/metabolismo , Inflamación/patología , Inflamación/genética , Interferón gamma/metabolismoRESUMEN
High-mobility group AT-hook 2 (HMGA2) is rearranged in various types of mesenchymal tumors, particularly lipomas. HMGA2 is also co-amplified with mouse double minute 2 (MDM2) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between HMGA2 and KITLG, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The HMGA2 breakpoint is in intron 3, a commonly observed location for HMGA2 rearrangements, while the KITLG breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of KITLG. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2, leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.
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Lipoma , Liposarcoma , Neoplasias de los Tejidos Conjuntivo y Blando , Humanos , Animales , Ratones , Liposarcoma/genética , Liposarcoma/patología , Lipoma/genética , Lipoma/patología , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Amplificación de GenesRESUMEN
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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Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Sustancia Gris , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Masculino , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Anciano , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Persona de Mediana Edad , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Imagen por Resonancia Magnética/métodosRESUMEN
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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Traditional ceramics or metals cannot simultaneously achieve ultrahigh strength and high electrical conductivity. The elemental carbon can form a variety of allotropes with entirely different physical properties, providing versatility for tuning mechanical and electrical properties in a wide range. Here, by precisely controlling the extent of transformation of amorphous carbon into diamond within a narrow temperature-pressure range, we synthesize an in situ composite consisting of ultrafine nanodiamond homogeneously dispersed in disordered multilayer graphene with incoherent interfaces, which demonstrates a Knoop hardness of up to ~53 GPa, a compressive strength of up to ~54 GPa and an electrical conductivity of 670-1,240 S m-1 at room temperature. With atomically resolving interface structures and molecular dynamics simulations, we reveal that amorphous carbon transforms into diamond through a nucleation process via a local rearrangement of carbon atoms and diffusion-driven growth, different from the transformation of graphite into diamond. The complex bonding between the diamond-like and graphite-like components greatly improves the mechanical properties of the composite. This superhard, ultrastrong, conductive elemental carbon composite has comprehensive properties that are superior to those of the known conductive ceramics and C/C composites. The intermediate hybridization state at the interfaces also provides insights into the amorphous-to-crystalline phase transition of carbon.
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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.
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Resistencia a la Sequía , Micorrizas , Simbiosis , Adaptación Fisiológica/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Hongos , Regulación de la Expresión Génica de las Plantas , Medicago truncatula/microbiología , Medicago truncatula/genética , Medicago truncatula/enzimología , Micorrizas/fisiología , Saccharomyces cerevisiae/genética , Simbiosis/genética , Simbiosis/fisiologíaRESUMEN
Copper and boron seldom engage in reaction at ambient pressure. The few reports on copper-doped boron compounds that exist in the literature often lack definitive stoichiometry. Here, we report successful synthesis of Cu_{2-δ}B_{25} single crystals (δâ¼0.03, indicating Cu understoichiometry) via a high-pressure melting method using copper and ß-rhombohedral boron as precursors. Crystals thus synthesized are characterized by a tetragonal boron sublattice, within which Cu atoms are either partially or fully situated at different interstices between B_{12} icosahedra. The crystals possess a high Vickers hardness of 26.5 GPa and an unusually high electrical conductivity of 1.19×10^{5} S/m-the highest conductivity among the icosahedron-based borides. Hall measurements reveal a notable p-n conduction type transition around 30 GPa. This transition, alongside the remarkable conductivity, is potentially modulated by the copper content and its valence states within the structure. The synthesis of Cu_{2-δ}B_{25} not only broadens the spectrum of hard materials but also opens new avenues for innovative modulation of electronic properties in boron-rich compounds, with promising technological implications.
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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.
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Adenoma , Hipopituitarismo , Neoplasias Hipofisarias , Radiocirugia , Humanos , Hipopituitarismo/etiología , Hipopituitarismo/epidemiología , Radiocirugia/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hipofisarias/cirugía , Adenoma/cirugía , Adenoma/patología , Adulto , Estudios Retrospectivos , Anciano , Factores de Riesgo , Estudios de Seguimiento , Adulto Joven , Adolescente , Incidencia , Anciano de 80 o más Años , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC, and accurate grading is crucial for prognosis and treatment selection. Biopsy is the reference standard for grading, but MRI methods can improve and complement the grading procedure. PURPOSE: Assess the performance of diffusion relaxation correlation spectroscopic imaging (DR-CSI) in grading ccRCC. STUDY TYPE: Prospective. SUBJECTS: 79 patients (age: 58.1 +/- 11.5 years; 55 male) with ccRCC confirmed by histopathology (grade 1, 7; grade 2, 45; grade 3, 18; grade 4, 9) following surgery. FIELD STRENGTH/SEQUENCE: 3.0 T MRI scanner. DR-CSI with a diffusion-weighted echo-planar imaging sequence and T2-mapping with a multi-echo spin echo sequence. ASSESSMENT: DR-CSI results were analyzed for the solid tumor regions of interest using spectrum segmentation with five sub-region volume fraction metrics (VA , VB , VC , VD , and VE ). The regulations for spectrum segmentation were determined based on the D-T2 spectra of distinct macro-components. Tumor size, voxel-wise T2, and apparent diffusion coefficient (ADC) values were obtained. Histopathology assessed tumor grade (G1-G4) for each case. STATISTICAL TESTS: One-way ANOVA or Kruskal-Wallis test, Spearman's correlation (coefficient, rho), multivariable logistic regression analysis, receiver operating characteristic curve analysis, and DeLong's test. Significance criteria: P < 0.05. RESULTS: Significant differences were found in ADC, T2, DR-CSI VB , and VD among the ccRCC grades. Correlations were found for ccRCC grade to tumor size (rho = 0.419), age (rho = 0.253), VB (rho = 0.553) and VD (rho = -0.378). AUC of VB was slightly larger than ADC in distinguishing low-grade (G1-G2) from high-grade (G3-G4) ccRCC (0.801 vs. 0.762, P = 0.406) and G1 from G2 to G4 (0.796 vs. 0.647, P = 0.175), although not significant. Combining VB , VD , and VE had better diagnostic performance than combining ADC and T2 for differentiating G1 from G2-G4 (AUC: 0.814 vs 0.643). DATA CONCLUSION: DR-CSI parameters are correlated with ccRCC grades, and may help to differentiate ccRCC grades. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Masculino , Persona de Mediana Edad , Anciano , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Estudios Prospectivos , Imagen por Resonancia Magnética , Imagen de Difusión por Resonancia Magnética/métodos , Clasificación del Tumor , Estudios RetrospectivosRESUMEN
The application of thermosensitive fluorescent supramolecular polymers in advanced optical materials, chemical sensors, artificial optical devices, and external stimulus responses remains underdeveloped. In this study, we introduced a novel method for constructing a mechanically interlocked fluorescent supramolecular polymer utilizing host-guest interactions, including C-H···π interactions and π-π stacking. This polymer exhibits outstanding temperature-sensitive fluorescence properties and is environmentally friendly due to its recyclability. Leveraging the polymer's fluorescence response at critical temperature ranges, we developed a high-temperature warning device. This device utilizes the temperature-sensitive fluorescence characteristic of the polymer to indicate dangerous temperature levels, thereby demonstrating its potential in practical safety applications.
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Mechanical properties of covalent materials can be greatly enhanced with strategy of nanostructuring. For example, the nanotwinned diamond with an isotropic microstructure of interweaved nanotwins and interlocked nanograins shows unprecedented isotropic mechanical properties. How the anisotropic microstructure would impact on the mechanical properties of diamond has not been fully investigated. Here, we report the synthesis of diamond from superaligned multiwalled carbon nanotube films under high pressure and high temperature. Structural characterization reveals preferentially oriented diamond nanotwin bundles with an average twin thickness of ca. 2.9 nm, inherited from the directional nanotubes. This diamond exhibits extreme mechanical anisotropy correlated with its microstructure (e.g., the average Knoop hardness values measured with the major axis of the indenter perpendicular and parallel to nanotwin bundles are 233 ± 8 and 129 ± 9 GPa, respectively). Molecular dynamics simulation reveals that, in the direction perpendicular to the nanotwin bundles, the dense twin boundaries significantly hinder the motion of dislocations under indentation, while such a resistance is much weaker in the direction along the nanotwin bundles. Current work verifies the hardening effect in diamond via nanostructuring. In addition, the mechanical properties can be further tuned (anisotropy) with microstructure design and modification.
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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.
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Cadmio , Flavonoides , Raíces de Plantas , Flavonoides/metabolismo , Cadmio/metabolismo , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Lignina/metabolismo , Morus/microbiología , Morus/metabolismo , Morus/genética , Estrés Fisiológico , Broussonetia/metabolismo , Broussonetia/microbiología , Broussonetia/genética , Micorrizas/fisiología , Glomeromycota/fisiología , Regulación de la Expresión Génica de las Plantas , Contaminantes del Suelo/metabolismo , HongosRESUMEN
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.
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Carcinoma de Células Renales , Imagen de Difusión por Resonancia Magnética , Neoplasias Renales , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Neoplasias Renales/diagnóstico por imagen , Masculino , Femenino , Imagen de Difusión por Resonancia Magnética/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Clasificación del Tumor , Anciano de 80 o más Años , Sensibilidad y EspecificidadRESUMEN
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.
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Neoplasias , Proteómica , Humanos , Proteómica/métodos , Neoplasias/metabolismo , Neoplasias/genética , Microambiente Tumoral/genética , Programas Informáticos , Biología Computacional/métodos , Proteoma/metabolismoRESUMEN
BACKGROUND AND PURPOSE: The sensory cortex is organized into "maps" that represent sensory space across cortical space. In primary visual cortex (V1) of highly visual mammals, multiple visual feature maps are organized into a functional architecture anchored by orientation domains: regions containing neurons preferring the same stimulus orientation. Although the pinwheel-like structure of orientation domains is well-characterized in the superficial cortical layers in dorsal regions of V1, the 3D shape of orientation domains spanning all 6 cortical layers and across dorsal and ventral regions of V1 has never been revealed. METHODS: We utilized an emerging research method in neuroscience, functional ultrasound imaging (fUS), to resolve the 3D structure of orientation domains throughout V1 in anesthetized female ferrets. fUS measures blood flow from which neuronal population activity is inferred with improved spatial resolution over fMRI. RESULTS: fUS activations in response to drifting gratings placed at multiple locations in visual space generated unique activation patterns in V1 and visual thalamus, confirming prior observations that fUS can resolve retinotopy. Iso-orientation domains, determined from clusters of activations driven by large oriented gratings, were cone-shaped and present in both dorsal and ventral regions of V1. The spacing between iso-orientation domains was consistent with spacing measured previously using optical imaging methods. CONCLUSIONS: Orientation domains are cones rather than columns. Their width and intra-domain distances may vary across dorsal and ventral regions of V1. These findings demonstrate the power of fUS at revealing 3D functional architecture in cortical regions not accessible to traditional surface imaging methods.
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Hurones , Corteza Visual , Humanos , Animales , Femenino , Hurones/fisiología , Corteza Visual Primaria , Corteza Visual/diagnóstico por imagen , Corteza Visual/fisiología , Células Fotorreceptoras Retinianas Conos , Ultrasonografía , Mapeo Encefálico , Estimulación LuminosaRESUMEN
Arbuscular mycorrhizal (AM) fungi can form beneficial associations with the most terrestrial vascular plant species. AM fungi not only facilitate plant nutrient acquisition but also enhance plant tolerance to various environmental stresses such as drought stress. However, the molecular mechanisms by which AM fungal mitogen-activated protein kinase (MAPK) cascades mediate the host adaptation to drought stimulus remains to be investigated. Recently, many studies have shown that virus-induced gene silencing (VIGS) and host-induced gene silencing (HIGS) strategies are used for functional studies of AM fungi. Here, we identify the three HOG1 (High Osmolarity Glycerol 1)-MAPK cascade genes RiSte11, RiPbs2 and RiHog1 from Rhizophagus irregularis. The expression levels of the three HOG1-MAPK genes are significantly increased in mycorrhizal roots of the plant Astragalus sinicus under severe drought stress. RiHog1 protein was predominantly localized in the nucleus of yeast in response to 1 M sorbitol treatment, and RiPbs2 interacts with RiSte11 or RiHog1 directly by pull-down assay. Importantly, VIGS or HIGS of RiSte11, RiPbs2 or RiHog1 hampers arbuscule development and decreases relative water content in plants during AM symbiosis. Moreover, silencing of HOG1-MAPK cascade genes led to the decreased expression of drought-resistant genes (RiAQPs, RiTPSs, RiNTH1 and Ri14-3-3) in the AM fungal symbiont in response to drought stress. Taken together, this study demonstrates that VIGS or HIGS of AM fungal HOG1-MAPK cascade inhibits arbuscule development and expression of AM fungal drought-resistant genes under drought stress.