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A major challenge in human genetics is to identify the molecular mechanisms of trait-associated and disease-associated variants. To achieve this, quantitative trait locus (QTL) mapping of genetic variants with intermediate molecular phenotypes such as gene expression and splicing have been widely adopted1,2. However, despite successes, the molecular basis for a considerable fraction of trait-associated and disease-associated variants remains unclear3,4. Here we show that ADAR-mediated adenosine-to-inosine RNA editing, a post-transcriptional event vital for suppressing cellular double-stranded RNA (dsRNA)-mediated innate immune interferon responses5-11, is an important potential mechanism underlying genetic variants associated with common inflammatory diseases. We identified and characterized 30,319 cis-RNA editing QTLs (edQTLs) across 49 human tissues. These edQTLs were significantly enriched in genome-wide association study signals for autoimmune and immune-mediated diseases. Colocalization analysis of edQTLs with disease risk loci further pinpointed key, putatively immunogenic dsRNAs formed by expected inverted repeat Alu elements as well as unexpected, highly over-represented cis-natural antisense transcripts. Furthermore, inflammatory disease risk variants, in aggregate, were associated with reduced editing of nearby dsRNAs and induced interferon responses in inflammatory diseases. This unique directional effect agrees with the established mechanism that lack of RNA editing by ADAR1 leads to the specific activation of the dsRNA sensor MDA5 and subsequent interferon responses and inflammation7-9. Our findings implicate cellular dsRNA editing and sensing as a previously underappreciated mechanism of common inflammatory diseases.
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Adenosina Desaminasa , Predisposición Genética a la Enfermedad , Enfermedades del Sistema Inmune , Inflamación , Edición de ARN , ARN Bicatenario , Adenosina/metabolismo , Adenosina Desaminasa/genética , Adenosina Desaminasa/metabolismo , Elementos Alu/genética , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Estudio de Asociación del Genoma Completo , Humanos , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/patología , Inmunidad Innata , Inflamación/genética , Inflamación/inmunología , Inflamación/patología , Inosina/metabolismo , Helicasa Inducida por Interferón IFIH1/metabolismo , Interferones/genética , Interferones/inmunología , Sitios de Carácter Cuantitativo/genética , Edición de ARN/genética , ARN Bicatenario/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
Iron-based redox-active minerals are ubiquitous in soils, sediments, and aquatic systems. Their dissolution is of great importance for microbial impacts on carbon cycling and the biogeochemistry of the lithosphere and hydrosphere. Despite its widespread significance and extensive prior study, the atomic-to-nanoscale mechanisms of dissolution remain poorly understood, particularly the interplay between acidic and reductive processes. Here, we use in situ liquid-phase-transmission electron microscopy (LP-TEM) and simulations of radiolysis to probe and control acidic versus reductive dissolution of akaganeite (ß-FeOOH) nanorods. Informed by crystal structure and surface chemistry, the balance between acidic dissolution at rod tips and reductive dissolution at rod sides was systematically varied using pH buffers, background chloride anions, and electron beam dose. We find that buffers, such as bis-tris, effectively inhibited dissolution by consuming radiolytic acidic and reducing species such as superoxides and aqueous electrons. In contrast, chloride anions simultaneously suppressed dissolution at rod tips by stabilizing structural elements while promoting dissolution at rod sides through surface complexation. Dissolution behaviors were systematically varied by shifting the balance between acidic and reductive attacks. The findings show LP-TEM combined with simulations of radiolysis effects can provide a unique and versatile platform for quantitatively investigating dissolution mechanisms, with implications for understanding metal cycling in natural environments and the development of tailored nanomaterials.
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Ginkgo (Ginkgo biloba L.) is one of the earliest extant species in seed plant phylogeny. Embryo development patterns can provide fundamental evidence for the origin, evolution, and adaptation of seeds. However, the architectural and morphological dynamics during embryogenesis in Ginkgo biloba (G. biloba) remain elusive. Herein, we obtained over 2200 visual slices from three stages of embryo development using micro-computed tomography imaging with improved staining methods. Based on 3D spatio-temporal pattern analysis, we found that a shoot apical meristem with seven highly differentiated leaf primordia, including apical and axillary leaf buds, is present in mature Ginkgo embryos. 3D rendering from the front, top, and side views showed two separate transport systems of tracheids located in the hypocotyl and cotyledon, representing a unique pattern of embryogenesis. Furthermore, the morphological dynamic analysis of secretory cavities indicated their strong association with cotyledons during development. In addition, we identified genes GbLBD25a (lateral organ boundaries domain 25a), GbCESA2a (cellulose synthase 2a), GbMYB74c (myeloblastosis 74c), GbPIN2 (PIN-FORMED 2) associated with vascular development regulation, and GbWRKY1 (WRKYGOK 1), GbbHLH12a (basic helix-loop-helix 12a), GbJAZ4 (jasmonate zim-domain 4) potentially involved in the formation of secretory cavities. Moreover, we found that flavonoid accumulation in mature embryos could enhance post-germinative growth and seedling establishment in harsh environments. Our 3D spatial reconstruction technique combined with multi-omics analysis opens avenues for investigating developmental architecture and molecular mechanisms during embryogenesis and lays the foundation for evolutionary studies of embryo development and maturation.
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Inorganic materials have essential roles in society, including in building construction, optical devices, mechanical engineering and as biomaterials1-4. However, the manufacture of inorganic materials is limited by classical crystallization5, which often produces powders rather than monoliths with continuous structures. Several precursors that enable non-classical crystallization-such as pre-nucleation clusters6-8, dense liquid droplets9,10, polymer-induced liquid precursor phases11-13 and nanoparticles14-have been proposed to improve the construction of inorganic materials, but the large-scale application of these precursors in monolith preparations is limited by availability and by practical considerations. Inspired by the processability of polymeric materials that can be manufactured by crosslinking monomers or oligomers15, here we demonstrate the construction of continuously structured inorganic materials by crosslinking ionic oligomers. Using calcium carbonate as a model, we obtain a large quantity of its oligomers (CaCO3)n with controllable molecular weights, in which triethylamine acts as a capping agent to stabilize the oligomers. The removal of triethylamine initiates crosslinking of the (CaCO3)n oligomers, and thus the rapid construction of pure monolithic calcium carbonate and even single crystals with a continuous internal structure. The fluid-like behaviour of the oligomer precursor enables it to be readily processed or moulded into shapes, even for materials with structural complexity and variable morphologies. The material construction strategy that we introduce here arises from a fusion of classic inorganic and polymer chemistry, and uses the same cross-linking process for the manufacture the materials.
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Carbonato de Calcio/química , Química Inorgánica , Ciencia de los Materiales/métodos , Polímeros/químicaRESUMEN
Cesium lead halide nanostructures have highly tunable optical and optoelectronic properties. Establishing precise control in forming perovskite single-crystal nanostructures is key to unlocking the full potential of these materials. However, studying the growth kinetics of colloidal cesium lead halides is challenging due to their sensitivity to light, electron beam, and environmental factors like humidity. In this study, in situ observations of CsPbBr3-particle dynamics were made possible through extremely low dose liquid cell transmission electron microscopy, showing that oriented attachment is the dominant pathway for the growth of single-crystal CsPbBr3 architectures from primary nanocubes. In addition, oriented assembly and fusion of ligand-stabilized cubic CsPbBr3 nanocrystals are promoted by electron beam irradiation or introduction of polar additives that both induce partial desorption of the original ligands and polarize the nanocube surfaces. These findings advance our understanding of cesium lead halide growth mechanisms, aiding the controlled synthesis of other perovskite nanostructures.
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In this work, we developed a visible-light-driven method for the selective synthesis of amides and N-acylureas from carboxylic acids and thioureas. This protocol was featured as avoidance of additional oxidants and transition metal catalysts, simple manipulations, low cost, broad substrate scope, and good functional group tolerance. As only oxygen serves as the oxidation reagent, this method provides a promising synthesis candidate for the formation of N-aryl amides and N-acylureas, including late-stage functionalization of complex pharmaceutical molecules and biologically active molecules.
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RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.
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Adenoma , Neoplasias Colorrectales , MicroARNs , Ácido Pirúvico , ARN Largo no Codificante , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , MicroARNs/genética , MicroARNs/metabolismo , Adenoma/genética , Adenoma/metabolismo , Adenoma/patología , Ácido Pirúvico/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Regulación Neoplásica de la Expresión Génica , Reprogramación MetabólicaRESUMEN
Ceria nanomaterials with facile CeIII/IV redox behavior are used in sensing, catalytic, and therapeutic applications, where inclusion of CeIII has been correlated with reactivity. Understanding assembly pathways of CeO2 nanoparticles (NC-CeO2) in water has been challenged by "blind" synthesis, including rapid assembly/precipitation promoted by heat or strong base. Here, we identify a layered phase denoted Ce-I with a proposed formula CeIV(OH)3(NO3)·xH2O (x ≈ 2.5), obtained by adding electrolytes to aqueous cerium ammonium nitrate (CAN) to force precipitation. Ce-I represents intermediate hydrolysis species between dissolved CAN and NC-CeO2, where CAN is a commonly used CeIV compound that exhibits unusual aqueous and organic solubility. Ce-I features Ce-(OH)2-Ce units, representing the first step of hydrolysis toward NC-CeO2 formation, challenging prior assertions about CeIV hydrolysis. Structure/composition of poorly crystalline Ce-I was corroborated by a pair distribution function, Ce-L3 XAS (X-ray absorption spectroscopy), compositional analysis, and 17O nuclear magnetic resonance spectroscopy. Formation of Ce-I and its transformation to NC-CeO2 is documented in solution by small-angle X-ray scattering (SAXS) and in the solid-state by transmission electron microscopy (TEM) and powder X-ray diffraction. Morphologies identified by TEM support form factor models for SAXS analysis, evidencing the incipient assembly of Ce-I. Finally, two morphologies of NC-CeO2 are identified. Sequentially, spherical NC-CeO2 particles coexist with Ce-I, and asymmetric NC-CeO2 with up to 35% CeIII forms at the expense of Ce-I, suggesting direct replacement.
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Supramolecular structures of matrix proteins in mineralizing tissues are known to direct the crystallization of inorganic materials. Here we demonstrate how such structures can be synthetically directed into predetermined patterns for which functionality is maintained. The study employs block copolymer lamellar patterns with alternating hydrophilic and hydrophobic regions to direct the assembly of amelogenin-derived peptide nanoribbons that template calcium phosphate nucleation by creating a low-energy interface. Results show that the patterned nanoribbons retain their ß-sheet structure and function and direct the formation of filamentous and plate-shaped calcium phosphate with high fidelity, where the phase, amorphous or crystalline, depends on the choice of mineral precursor and the fidelity depends on peptide sequence. The common ability of supramolecular systems to assemble on surfaces with appropriate chemistry combined with the tendency of many templates to mineralize multiple inorganic materials implies this approach defines a general platform for bottom-up-patterning of hybrid organic-inorganic materials.
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Biomimética , Nanotubos de Carbono , Polímeros/química , Minerales , Fosfatos de Calcio/química , Péptidos/químicaRESUMEN
Aqueous zinc ion batteries (AZIBs) have emerged as a promising battery technology due to their excellent safety, high capacity, low cost, and eco-friendliness. However, the cycle life of AZIBs is limited by severe side reactions and zinc dendrite growth on the zinc electrode surface, hindering large-scale application. Here, an electrolyte optimization strategy utilizing the simplest dipeptide glycylglycine (Gly-Gly) additive is first proposed. Theoretical calculations and spectral analysis revealed that, due to the strong interaction between the amino group and Zn atoms, Gly-Gly preferentially adsorbs on zinc's surface, constructing a stable and adaptive interfacial layer that inhibits zinc side reactions and dendrite growth. Furthermore, Gly-Gly can regulate zinc ion solvation, leading to a deposition mode shift from dendritic to lamellar and limiting two-dimensional dendrite diffusion. The symmetric cell with the addition of a 20 g/L Gly-Gly additive exhibits a cycle life of up to 1100 h. Under a high current density of 10 mA cm-2, a cycle life of 750 cycles further demonstrates the reliable adaptability of the interfacial layer. This work highlights the potential of Gly-Gly as a promising solution for improving the performance of AZIBs.
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Metastasis accounts for most cancer-associated deaths; yet, this complex process remains poorly understood, particularly the relationship between distant metastasis and primary site-derived cells. Here, we modified the classical MMTV-PyMT breast carcinoma model to trace the fate of mammary-derived carcinoma cells. We show that within the lung, when the metastatic breast carcinoma cells are conditionally depleted, transformed lung epithelial cells generate new metastases. Metastatic breast carcinoma cells transmit H19 long noncoding (lnc) RNA to lung epithelial cells through exosomes. SF3B1 bearing mutations at arginine-625 alternatively splices H19 lncRNA in lung epithelial cells, which selectively acts like a molecular sponge to sequester let-7a and induces Myc upregulation. Under the conditional elimination of primary site-derived breast carcinoma cells, lung malignant cells expressing the mutated SF3B1 splice variant dominate the newly created tumors. Our study suggests that these new carcinoma cells originating from within the colonized organ can replace the primary site-derived malignant cells whenever their expansion is abrogated using an inducible diphtheria toxin receptor in our designed system. These findings should call for a better understanding of metastatic tumors with the specific origin during cancer metastasis.
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Neoplasias de la Mama , Neoplasias Pulmonares , Neoplasias Mamarias Animales , ARN Largo no Codificante , Animales , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Empalme Alternativo , Mama/patología , Pulmón/patología , Neoplasias Mamarias Animales/patología , Neoplasias Pulmonares/secundario , Factores de Transcripción/genética , Línea Celular TumoralRESUMEN
Cytosolic recognition of microbial DNA in macrophages results in the activation of the interferon (IFN)-dependent antiviral innate immunity. Here, we examined whether activating DNA sensors in peripheral blood monocyte-derived macrophages (MDMs) can inhibit human immunodeficiency virus (HIV). We observed that the stimulation of MDMs with poly(dA:dT) or poly(dG:dC) (synthetic ligands for the DNA sensors) inhibited HIV infection and replication. MDMs treated with poly(dA:dT) or poly(dG:dC) expressed higher levels of both type I and type III IFNs than untreated cells. Activation of the DNA sensors in MDMs also induced the expression of the multiple intracellular anti-HIV factors, including IFN-stimulated genes (ISGs: ISG15, ISG56, Viperin, OAS2, GBP5, MxB, and Tetherin) and the HIV restriction microRNAs (miR-29c, miR-138, miR-146a, miR-155, miR-198, and miR-223). In addition, the DNA sensor activation of MDM upregulated the expression of the CC chemokines (RANTES, MIP-1α, MIP-1ß), the ligands for HIV entry coreceptor CCR5. These observations indicate that the cytosolic DNA sensors have a protective role in the macrophage intracellular immunity against HIV and that targeting the DNA sensors has therapeutic potential for immune activation-based anti-HIV treatment.
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Infecciones por VIH , VIH-1 , MicroARNs , Humanos , Infecciones por VIH/metabolismo , VIH-1/fisiología , Células Cultivadas , Macrófagos , MicroARNs/genética , MicroARNs/metabolismo , ADN/metabolismo , Replicación ViralRESUMEN
As a key immune cell in the brain, microglia are essential for protecting the central nervous system (CNS) from viral infections, including HIV. Microglia possess functional Toll-like receptor 3 (TLR3), a key viral sensor for activating interferon (IFN) signaling pathway-mediated antiviral immunity. We, therefore, studied the effect of poly (I:C), a synthetic ligand of TLR3, on the activation of the intracellular innate immunity against HIV in human iPSC-derived microglia (iMg). We found that poly (I:C) treatment of iMg effectively inhibits HIV infection/replication at both mRNA and protein levels. Investigations of the mechanisms revealed that TLR3 activation of iMg by poly (I:C) induced the expression of both type I and type III IFNs. Compared with untreated cells, the poly (I:C)-treated iMg expressed significantly higher levels of IFN-stimulated genes (ISGs) with known anti-HIV activities (ISG15, MxB, Viperin, MxA, and OAS-1). In addition, TLR3 activation elicited the expression of the HIV entry coreceptor CCR5 ligands (CC chemokines) in iMg. Furthermore, the transcriptional profile analysis showed that poly (I:C)-treated cells had the upregulated IFN signaling genes (ISG15, ISG20, IFITM1, IFITM2, IFITM3, IFITM10, APOBEC3A, OAS-2, MxA, and MxB) and the increased CC chemokine signaling genes (CCL1, CCL2, CCL3, CCL4, and CCL15). These observations indicate that TLR3 is a potential therapy target for activating the intracellular innate immunity against HIV infection/replication in human microglial cells. Therefore, further studies with animal models and clinical specimens are necessary to determine the role of TLR3 activation-driven antiviral response in the control and elimination of HIV in infected host cells.
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Infecciones por VIH , Células Madre Pluripotentes Inducidas , Microglía , Receptor Toll-Like 3 , Humanos , Células Cultivadas , Inmunidad Innata , Microglía/virología , Poli I-C/farmacología , Receptor Toll-Like 3/genéticaRESUMEN
We propose a simulation method for a multireflector terahertz imaging system. The description and verification of the method are based on an existing active bifocal terahertz imaging system at 0.22 THz. Using the phase conversion factor and angular spectrum propagation, the computation of the incident and received fields requires only a simple matrix operation. The phase angle is used to calculate the ray tracking direction, and the total optical path is used to calculate the scattering field of defective foams. Compared with the measurements and simulations of aluminum disks and defective foams, the validity of the simulation method is confirmed in the field of view of 50â cm × 90â cm at 8 m. This work aims to develop better imaging systems by predicting their imaging behavior for different targets before manufacturing.
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Accelerated urbanization and industrialization have led to an alarming increase in the generation of wastewater with complex chemical contents. Industrial wastewaters are often a primary source of water contamination. The chemical characterization of different industrial wastewater types is an essential task to interpret the chemical fingerprints of wastewater to identify pollution sources and develop efficient water treatment strategies. In this study, we conduct a non-target chemical analysis for the source characterization of different industrial wastewater samples collected from a chemical industrial park (CIP) located in southeast China. The chemical screening identified volatile and semi-volatile organic compounds that included dibutyl phthalate at a maximum concentration of 13.4 µg/L and phthalic anhydride at 35.9 µg/L. Persistent, mobile, and toxic (PMT) substances among the detected organic compounds were identified and prioritized as high-concern contaminants given their impact on drinking water resources. Moreover, a source analysis of the wastewater collected from the wastewater outlet station indicated that the dye production industry contributed the largest quantities of toxic contaminates (62.6%), and this result was consistent with the ordinary least squares and heatmap results. Thus, our study utilized a combined approach of a non-target chemical analysis, a pollution source identification method, and a PMT assessment of different industrial wastewater samples collected from the CIP. The results of the chemical fingerprints of different industrial wastewater types as well as the results of the PMT assessment benefit risk-based wastewater management and source reduction strategies.
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Contaminantes Ambientales , Compuestos Orgánicos Volátiles , Contaminantes Químicos del Agua , Contaminantes Ambientales/análisis , Aguas Residuales , Contaminantes Químicos del Agua/análisis , ChinaRESUMEN
OBJECTIVE: This study aimed to investigate the correlation between apparent diffusion coefficient (ADC) and the Ki-67 proliferation index with the pathologic grades of pediatric glioma and to compare their diagnostic performance in differentiating grades of pediatric glioma. PATIENTS AND METHODS: Magnetic resonance imaging examinations and histopathologies of 121 surgically treated pediatric gliomas (87 low-grade gliomas [LGGs; grades 1 and 2] and 34 high-grade gliomas [HGGs; grades 3 and 4]) were retrospectively reviewed. The mean tumor ADC (ADCmean), minimum tumor ADC (ADCmin), tumor/normal brain ADC ratio (ADC ratio), and value of the Ki-67 proliferation index of LGGs and HGGs were compared. Correlation coefficients were calculated for ADC parameters and Ki-67 values. The receiver operating characteristic curve was used to determine the diagnostic value of ADCmean, ADCmin, ADC ratio, and Ki-67 proliferation index for differentiating LGGs and HGGs. RESULTS: The ADC values were significantly negatively correlated with glioma grade, and the Ki-67 proliferation index had a significant positive correlation with glioma grade. A significant negative correlation was observed between ADCmean and Ki-67 proliferation index, between ADCmin and Ki-67 proliferation index, and between ADC ratio and Ki-67 proliferation index. The receiver operating characteristic analysis demonstrated moderate to good accuracy for ADCmean in discriminating LGGs from HGGs (area under the curve [AUC], 0.875; sensitivity, 79.3%; specificity, 82.4%; accuracy, 80.2%; positive predictive value [PPV], 92.0%; and negative predictive value [NPV], 60.9% [cutoff value, 1.187] [×10-3 mm2/s]). Minimum tumor ADC showed very good to excellent accuracy with AUC of 0.946, sensitivity of 86.2%, specificity of 94.1%, accuracy of 88.4%, PPV of 97.4%, and NPV of 72.7% (cutoff value, 0.970) (×10-3 mm2/s). The ADC ratio showed moderate to good accuracy with AUC of 0.854, sensitivity of 72.4%, specificity of 88.2%, accuracy of 76.9%, PPV of 94.0%, and NPV of 55.6% (cutoff value, 1.426). For the parameter of the Ki-67 proliferation index, in discriminating LGGs from HGGs, very good to excellent diagnostic accuracy was observed (AUC, 0.962; sensitivity, 94.1%; specificity, 89.7%; accuracy, 90.9%; PPV, 97.5%; and NPV, 78.0% [cutoff value, 7]). CONCLUSIONS: Apparent diffusion coefficient parameters and the Ki-67 proliferation index were significantly correlated with histological grade in pediatric gliomas. Apparent diffusion coefficient was closely correlated with the proliferative potential of pediatric gliomas. In addition, ADCmin showed superior performance compared with ADCmean and ADC ratio in differentiating pediatric glioma grade, with a close diagnostic efficacy to the Ki-67 proliferation index.
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Neoplasias Encefálicas , Imagen de Difusión por Resonancia Magnética , Glioma , Niño , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Proliferación Celular , Imagen de Difusión por Resonancia Magnética/métodos , Glioma/diagnóstico por imagen , Glioma/patología , Antígeno Ki-67 , Clasificación del Tumor , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Organisms use inorganic ions and macromolecules to regulate crystallization from amorphous precursors, endowing natural biominerals with complex morphologies and enhanced properties. The mechanisms by which modifiers enable these shape-preserving transformations are poorly understood. We used in situ liquid-phase transmission electron microscopy to follow the evolution from amorphous calcium carbonate to calcite in the presence of additives. A combination of contrast analysis and infrared spectroscopy shows that Mg ions, which are widely present in seawater and biological fluids, alter the transformation pathway in a concentration-dependent manner. The ions bring excess (structural) water into the amorphous bulk so that a direct transformation is triggered by dehydration in the absence of morphological changes. Molecular dynamics simulations suggest Mg-incorporated water induces structural fluctuations, allowing transformation without the need to nucleate a separate crystal. Thus, the obtained calcite retains the original morphology of the amorphous state, biomimetically achieving the morphological control of crystals seen in biominerals.
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Aging is a universal property of multicellular organisms. Although some tree species can live for centuries or millennia, the molecular and metabolic mechanisms underlying their longevity are unclear. To address this, we investigated age-related changes in the vascular cambium from 15- to 667-y-old Ginkgo biloba trees. The ring width decreased sharply during the first 100 to 200 y, with only a slight change after 200 y of age, accompanied by decreasing numbers of cambial cell layers. In contrast, average basal area increment (BAI) continuously increased with aging, showing that the lateral meristem can retain indeterminacy in old trees. The indole-3-acetic acid (IAA) concentration in cambial cells decreased with age, whereas the content of abscisic acid (ABA) increased significantly. In addition, cell division-, cell expansion-, and differentiation-related genes exhibited significantly lower expression in old trees, especially miR166 and HD-ZIP III interaction networks involved in cambial activity. Disease resistance-associated genes retained high expression in old trees, along with genes associated with synthesis of preformed protective secondary metabolites. Comprehensive evaluation of the expression of genes related to autophagy, senescence, and age-related miRNAs, together with analysis of leaf photosynthetic efficiencies and seed germination rates, demonstrated that the old trees are still in a healthy, mature state, and senescence is not manifested at the whole-plant level. Taken together, our results reveal that long-lived trees have evolved compensatory mechanisms to maintain a balance between growth and aging processes. This involves continued cambial divisions, high expression of resistance-associated genes, and continued synthetic capacity of preformed protective secondary metabolites.
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Cámbium/metabolismo , Ginkgo biloba/crecimiento & desarrollo , Árboles/crecimiento & desarrollo , Ácido Abscísico/metabolismo , Cámbium/citología , Ginkgo biloba/genética , Ginkgo biloba/metabolismo , Ácidos Indolacéticos/metabolismo , Reguladores del Crecimiento de las Plantas/biosíntesis , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Tiempo , Árboles/genética , Árboles/metabolismoRESUMEN
Nuclear factor Y (NF-Y) transcription factors play an essential role in regulating plant growth, development, and stress responses. Despite extensive research on the NF-Y gene family across various species, the knowledge regarding the NF-Y family in Ginkgo biloba remains unknown. In this study, we identified a total of 25 NF-Y genes (seven GbNF-YAs, 12 GbNF-YBs, and six GbNF-YCs) in the G. biloba genome. We characterized the gene structure, conserved motifs, multiple sequence alignments, and phylogenetic relationships with other species (Populus and Arabidopsis). Additionally, we conducted a synteny analysis, which revealed the occurrence of segment duplicated NF-YAs and NF-YBs. The promoters of GbNF-Y genes contained cis-acting elements related to stress response, and miRNA-mRNA analysis showed that some GbNF-YAs with stress-related cis-elements could be targeted by the conserved miRNA169. The expression of GbNF-YA genes responded to drought, salt, and heat treatments, with GbNF-YA6 showing significant upregulation under heat and drought stress. Subcellular localization indicated that GbNF-YA6 was located in both the nucleus and the membrane. Overexpressing GbNF-YA6 in ginkgo callus significantly induced the expression of heat-shock factors (GbHSFs), and overexpressing GbNF-YA6 in transgenic Arabidopsis enhanced its heat tolerance. Additionally, Y2H assays demonstrated that GbNF-YA6 could interact with GbHSP at the protein level. Overall, our findings offer novel insights into the role of GbNF-YA in enhancing abiotic stress tolerance and warrant further functional research of GbNF-Y genes.
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Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.