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Nutrients and energy have emerged as central modulators of developmental programmes in plants and animals1-3. The evolutionarily conserved target of rapamycin (TOR) kinase is a master integrator of nutrient and energy signalling that controls growth. Despite its key regulatory roles in translation, proliferation, metabolism and autophagy2-5, little is known about how TOR shapes developmental transitions and differentiation. Here we show that glucose-activated TOR kinase controls genome-wide histone H3 trimethylation at K27 (H3K27me3) in Arabidopsis thaliana, which regulates cell fate and development6-10. We identify FERTILIZATION-INDEPENDENT ENDOSPERM (FIE), an indispensable component of Polycomb repressive complex 2 (PRC2), which catalyses H3K27me3 (refs. 6-8,10-12), as a TOR target. Direct phosphorylation by TOR promotes the dynamic translocation of FIE from the cytoplasm to the nucleus. Mutation of the phosphorylation site on FIE abrogates the global H3K27me3 landscape, reprogrammes the transcriptome and disrupts organogenesis in plants. Moreover, glucose-TOR-FIE-PRC2 signalling modulates vernalization-induced floral transition. We propose that this signalling axis serves as a nutritional checkpoint leading to epigenetic silencing of key transcription factor genes that specify stem cell destiny in shoot and root meristems and control leaf, flower and silique patterning, branching and vegetative-to-reproduction transition. Our findings reveal a fundamental mechanism of nutrient signalling in direct epigenome reprogramming, with broad relevance for the developmental control of multicellular organisms.
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Arabidopsis , Glucose , Alvo Mecanístico do Complexo 2 de Rapamicina , Fosfatidilinositol 3-Quinases , Desenvolvimento Vegetal , Complexo Repressor Polycomb 2 , Proteínas Repressoras , Transdução de Sinais , Arabidopsis/embriologia , Arabidopsis/enzimologia , Arabidopsis/genética , Arabidopsis/metabolismo , Diferenciação Celular/genética , Linhagem da Célula/genética , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Glucose/metabolismo , Histonas/química , Histonas/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Mutação , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Desenvolvimento Vegetal/genética , Complexo Repressor Polycomb 2/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genéticaRESUMO
Autoluminescent plants have been genetically modified to express the fungal bioluminescence pathway (FBP). However, a bottleneck in precursor production has limited the brightness of these luminescent plants. Here, we demonstrate the effectiveness of utilizing a computational model to guide a multiplex five-gene-silencing strategy by an artificial microRNA array to enhance caffeic acid and hispidin levels in plants. By combining loss-of-function-directed metabolic flux with a tyrosine-derived caffeic acid pathway, we achieved substantially enhanced bioluminescence levels. We successfully generated eFBP2 plants that emit considerably brighter bioluminescence for naked-eye reading by integrating all validated DNA modules. Our analysis revealed that the luminous energy conversion efficiency of the eFBP2 plants is currently very low, suggesting that luminescence intensity can be improved in future iterations. These findings highlight the potential to enhance plant luminescence through the integration of biological and information technologies.
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In this paper, we present the bit error rate (BER) performance of the underwater wireless optical communication (UWOC) systems using the optical space shift keying (OSSK) on the gamma-gamma turbulent fading channel, which also considers pointing errors and channel estimation errors. Firstly, we develop the new expressions for the probability density function (PDF) based on the Gamma-Gamma distribution with error factors. Subsequently, we analyze the statistical characteristic of the difference in attenuation coefficients between two channels in the OSSK system, by which we provide analytical results for evaluating the average BER performance. The results show that the effective improvement of spectral efficiency (SE) and BER performance is achieved by rationally allocating the number of lasers and detectors in the system. The OSSK-UWOC system performs better when a narrow beam waist is used. Furthermore, the presence of channel estimation error brings the BER performance advantage to the system, and the system with a high channel estimation error (ρ = 0.7) shows a 4â dB improvement in signal-to-noise ratio (SNR) gain compared to the system with a low channel estimation error (ρ = 0.95). The findings in this paper can be used for the UWOC system design.
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This paper investigates the propagation of Gaussian array beams (GABs) through seawater-to-air in the presence of oceanic turbulence, atmospheric turbulence, and wave foams. Specifically, we focus on the intensity distribution of diverse typical GAB structures (ring, multi-ring, and rectangle). Then, an innovative intensity analysis model to calculate the average intensity in each medium is proposed. Moreover, we experimentally verify the proposed method by examining the intensity fading characteristic of Gaussian beams in the seawater-to-air path. Our results show that the peak intensity is primarily affected by the refraction in the ocean and foam layer, rather than air layer. The difference of theoretical and experimental values are less than 0.13 for the peak intensity. Moreover, the intensity distributions are more significantly affected by ocean turbulence but less influenced by wind speed.
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The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.
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Regeneração Óssea , Células-Tronco Mesenquimais , Osteogênese , Poliésteres , Engenharia Tecidual , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Ratos , Regeneração Óssea/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Engenharia Tecidual/métodos , Poliésteres/química , Diferenciação Celular , Ratos Sprague-Dawley , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Células Cultivadas , Proliferação de Células , Crânio/lesões , Crânio/patologia , Durapatita/química , Durapatita/farmacologiaRESUMO
To determine the H-abstraction reaction probabilities of H/O/OH radicals with a polypropylene (PP) surface, a first-principles calculation was performed based on the DLPNO-CCSD(T)/CBS//M06-2X-D3/def-TZVP theory level. The PP chain model used in this study was 2,4,6-trimethylheptane. The rate constants of the H/O/OH radicals with the isolated PP chain model were calculated based on the conventional transition-state theory. By comparing the experimental values and considering the error factors and their compensation, it was concluded that the orders of magnitude of the predicted rate constants were accurate. The resulting rate constants were converted to reaction probabilities between the H/O/OH radicals and the PP surface. The method used in this study is applicable for obtaining theoretical values of surface reaction probabilities based on first-principles calculations. The calculation at the DLPNO-CCSD(T)/CBS theory level has high accuracy but consumes a large amount of computational resources. The study also demonstrated that the double-hybrid functionals, wB97x-2-D3(BJ) and rev-DSD-PBEP86-D3(BJ), with a 3-ζ or 4-ζ basis set, could reproduce the electronic energy values obtained from DLPNO-CCSD(T)/CBS while using only approximately 1/100 of the computational resources required by the latter under our computer configuration.
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Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.
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Ácidos Nucleicos , Sarcopenia , Humanos , Idoso , Camundongos , Animais , Sarcopenia/tratamento farmacológico , Sarcopenia/patologia , Ácidos Nucleicos/uso terapêutico , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Apoptose , Mitocôndrias/patologiaRESUMO
Rational fabrication of core-shell photocatalysts to hamper the charge recombination is extraordinarily essential to enhance photocatalytic activity. In this work, core-shell Ag@NH2-UiO-66 (Ag@NU) Schottky heterojunctions with low Ag content (1 wt%) were constructed by a two-step solvothermal method and adopted for Cr(VI) reduction under LED light. Typically, the one with the Ag: NH2-UiO-66 mass ratio (1 : 100) led to 100% Cr(VI) removal within 1 h, superior to bare NH2-UiO-66 and Ag/NH2-UiO-66 (Ag was directly decorated on NH2-UiO-66 surface). The enhanced photocatalytic activity was related to the migration of the electrons on the CB of NH2-UiO-66 to Ag NPs through a Schottky barrier, and thus the undesired charge carriers recombination was avoided. This result was also evidenced by Density functional theory (DFT) calculations. The computational simulations indicate that the introduction of Ag effectively narrowed the band gap of NH2-UiO-66, facilitating the transfer of photo-generated electrons, expanding the light absorption area, and significantly enhancing photocatalytic efficiency. Most importantly, such a core-shell structure can inhibit the formation of â¢O2-, letting the direct Cr(VI) reduction by photo-excited e-. In addition, this structure can also protect Ag from being oxidized by O2. Ten cyclic tests evidenced the Ag@NU had excellent chemical and structural stability. This research offers a novel strategy for regulating the Cr(VI) reduction by establishing core-shell photocatalytic materials.
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Cromo , Catálise , Cromo/química , Prata/químicaRESUMO
In this study, we report the successful development of a novel high-sensitivity intensity-based Surface Plasmon Resonance imaging (SPRi) biosensor and its application for detecting molecular interactions. By optimizing the excitation wavelength and employing a wavelength division multiplexing (WDM) algorithm, the system can determine the optimal excitation wavelength based on the initial refractive index of the sample without adjusting the incidence angle. The experimental results demonstrate that the refractive index resolution of the system reaches 1.77×10-6 RIU. Moreover, it can obtain the optimal excitation wavelength for samples with an initial refractive index in the range of 1.333 to 1.370 RIU and accurately monitor variations within the range of 0.0037 RIU without adjusting the incidence angle. Additionally, our new SPRi technique realized real-time detection of high-throughput biomolecular binding processes, enabling analysis of kinetic parameters. This research is expected to advance the development of more accurate SPRi technologies for molecular interaction analysis.
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Técnicas Biossensoriais , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Técnicas Biossensoriais/métodos , Algoritmos , Refratometria , Ensaios de Triagem em Larga Escala/métodos , CinéticaRESUMO
Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.
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Movimento Celular , Proliferação de Células , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Xantofilas , Humanos , Serina-Treonina Quinases TOR/metabolismo , Xantofilas/farmacologia , Xantofilas/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Metástase Neoplásica , Simulação de Acoplamento MolecularRESUMO
This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.
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Ferroptose , Heme Oxigenase-1 , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Xantofilas , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Ferroptose/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/química , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Linhagem Celular Tumoral , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Receptores da Transferrina/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Superóxido Dismutase/metabolismo , Regulação para Baixo/efeitos dos fármacos , Antígenos CDRESUMO
Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.
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Lesões Encefálicas Traumáticas , Gliose , Camundongos , Animais , Gliose/genética , Gliose/metabolismo , Gliose/patologia , Neurônios/metabolismo , Lesões Encefálicas Traumáticas/terapia , Encéfalo/metabolismo , RegeneraçãoRESUMO
Resistance genes (R genes) are a class of genes that are immune to a wide range of diseases and pests. In planta, NLR genes are essential components of the innate immune system. Currently, genes belonging to NLR family have been found in a number of plant species, but little is known in peach. Here, 286 NLR genes were identified on peach genome by using their homologous genes in Arabidopsis thaliana as queries. These 286 NLR genes contained at least one NBS domain and LRR domain. Phylogenetic and N-terminal domain analysis showed that these NLRs could be separated into four subfamilies (I-IV) and their promoters contained many cis-elements in response to defense and phytohormones. In addition, transcriptome analysis showed that 22 NLR genes were up-regulated after infected by Green Peach Aphid (GPA), and showed different expression patterns. This study clarified the NLR gene family and their potential functions in aphid resistance process. The candidate NLR genes might be useful in illustrating the mechanism of aphid resistance in peach.
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Afídeos , Proteínas de Arabidopsis , Arabidopsis , Animais , Proteínas de Arabidopsis/genética , Afídeos/fisiologia , Leucina/genética , Filogenia , Arabidopsis/genética , Nucleotídeos/metabolismoRESUMO
The fungal bioluminescence pathway (FBP) was identified from glowing fungi, which releases self-sustained visible green luminescence. However, weak bioluminescence limits the potential application of the bioluminescence system. Here, we screened and characterized a C3'H1 (4-coumaroyl shikimate/quinate 3'-hydroxylase) gene from Brassica napus, which efficiently converts p-coumaroyl shikimate to caffeic acid and hispidin. Simultaneous expression of BnC3'H1 and NPGA (null-pigment mutant in A. nidulans) produces more caffeic acid and hispidin as the natural precursor of luciferin and significantly intensifies the original fungal bioluminescence pathway (oFBP). Thus, we successfully created enhanced FBP (eFBP) plants emitting 3 × 1011 photons/min/cm2 , sufficient to illuminate its surroundings and visualize words clearly in the dark. The glowing plants provide sustainable and bio-renewable illumination for the naked eyes, and manifest distinct responses to diverse environmental conditions via caffeic acid biosynthesis pathway. Importantly, we revealed that the biosynthesis of caffeic acid and hispidin in eFBP plants derived from the sugar pathway, and the inhibitors of the energy production system significantly reduced the luminescence signal rapidly from eFBP plants, suggesting that the FBP system coupled with the luciferin metabolic flux functions in an energy-driven way. These findings lay the groundwork for genetically creating stronger eFBP plants and developing more powerful biological tools with the FBP system.
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Engenharia Metabólica , Plantas , LuciferinasRESUMO
To improve the measurement accuracy of interferometer displacement measurement systems, this study analyzes the characteristics of the interference signal to identify sources of nonlinear errors and develops compensation strategies. Specifically, a model is established for the nonlinear errors of the interferometer, which can be attributed to a laser and polarizing beam splitter (PBS). Following that, the dual orthogonal lock-in amplification algorithm is used to separate and compensate for the frequency uncertainty and amplitude errors. Additionally, a real-time compensation algorithm based on ellipse fitting is proposed to compensate for errors caused by the PBS and the uncertainty of amplitude caused by the light source. Experimental results demonstrate that the peak-to-peak value of the compensated nonlinear error is reduced from 11.62 nm to 5.37 nm.
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Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca2+-sensor protein kinases (CPKs) as master regulators that orchestrate primary nitrate responses. A chemical switch with the engineered mutant CPK10(M141G) circumvents embryo lethality and enables conditional analyses of cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated regulatory and developmental programs. Nitrate-coupled CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors to specify the reprogramming of gene sets for downstream transcription factors, transporters, nitrogen assimilation, carbon/nitrogen metabolism, redox, signalling, hormones and proliferation. Conditional cpk10 cpk30 cpk32 and nlp7 mutants similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture.
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Amidoidrolases/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Cálcio/metabolismo , Nitratos/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais , Amidoidrolases/genética , Sequência de Aminoácidos , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Biomassa , Sinalização do Cálcio , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/química , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Carbono/metabolismo , Reprogramação Celular , Alimentos , Regulação da Expressão Gênica de Plantas , Nitrogênio/metabolismo , Oxirredução , Fosforilação , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Proteínas Quinases/química , Proteínas Quinases/genética , Transcrição Gênica , TranscriptomaRESUMO
BACKGROUND: The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. RESULTS: We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). CONCLUSIONS: Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy.
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Glioma , MicroRNAs , Células Supressoras Mieloides , Humanos , Retroalimentação , Imunossupressores , MicroRNAs/genética , Microambiente Tumoral , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Exossomos/genética , Exossomos/metabolismo , Fator de Transcrição Sp1RESUMO
OBJECTIVE: Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy. METHODS: A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups. RESULTS: A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2, ranging from 12.4 kg/m2 to 28.3 kg/m2. Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery. CONCLUSION: Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible.
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Epilepsia , Obesidade Infantil , Masculino , Feminino , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Estudos Retrospectivos , Obesidade Infantil/complicações , Perda Sanguínea Cirúrgica , Sobrepeso/complicações , Epilepsia/complicações , Epilepsia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Índice de Massa Corporal , Resultado do TratamentoRESUMO
Coal gangue (CG), one of the world's largest industrial solid wastes produced during coal mining, is extremely difficult to be used owing to its combined contents of clay minerals and organic macromolecules. This study explored a novel process of degrading the harmful organic compounds in the CG into humic acid using a biological method characterized by scanning electron microscope-energy dispersive spectrometer, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and elemental analyzer. The results reveal that adding selected Bacillus sp. to the CG for 40 days can increase the humic acid content by ~ 17 times, reaching 17338.17 mg/kg, which is also the best level for promoting plant growth. FTIR and XPS spectra show that the organic compounds in the CG transforms primarily from C=C to C=O, COOH, and O-H groups, indicating that the organic compounds are gradually oxidized and activated, improving the humic acid concentration of soil. In addition, Bacillus sp. decreases pH and benzo[a]pyrene contents, and increases the content of available nutrients. After microbial degradation, coal gangue can be turned into ecological restoration materials.
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Bacillus , Carvão Mineral , Carvão Mineral/análise , Substâncias Húmicas/análise , Compostos Orgânicos , Solo , Resíduos Industriais/análiseRESUMO
Objective: The purpose of this retrospective cohort study was to evaluate clinical outcomes in high-risk patients with symptomatic intracranial atherosclerotic stenosis (sICAS) resulting from plaque enhancement who underwent balloon dilation or stent implantation. Plaque features were identified based on high-resolution magnetic resonance vessel wall imaging (HRMR-VWI). Methods: A total of 37 patients with sICAS (degree of stenosis ≥70%) were enrolled between January 2018 and March 2022 at a single center. All patients underwent HRMR-VWI and received standard drug treatment after hospital admission. The patients were divided into 2 groups based on whether they underwent interventional treatment (n = 18) or non-interventional treatment (n = 19). The grade of enhancement and enhancement rate (ER) of culprit plaque were evaluated using 3D-HRMR-VWI. The risk of symptom recurrence was compared between the 2 groups during follow-up. Results: There was no statistical difference between the intervention and non-intervention groups in the rate and type of enhancement. Median clinical follow-up time was 17.8 (10.0 to 26.0) months and median follow-up time was 3.6 (3.1 to 6.2) months. In the intervention group, 2 patients had stent restenosis, but no stroke or transient ischemia attacks (TIAs) occurred. In contrast, 1 patient in the non-intervention group had an ischemic stroke and 4 patients had TIAs. The incidence of the primary outcome was lower in the intervention group than in the non-intervention group (0 vs 26.3%; P = .046). Conclusions: High-resolution magnetic resonance intracranial vessel wall imaging (HR MR-IVWI) can be used to identify vulnerable plaque features. It is safe and effective in high-risk patients with sICAS with responsible plaque enhancement to undergo intravascular intervention combined with standard drug therapy. Further studies are needed to analyze the link between plaque enhancement and symptom recurrence in the medication group at baseline.