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1.
Adv Mater ; : e2402445, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583077

RESUMO

Brain disorders represent a significant challenge in medical science due to the formidable blood-brain barrier (BBB), which severely limits the penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into the innovative realm of biomimetic nanodelivery systems, including stem cell-derived nanoghosts, tumor cell membrane-coated nanoparticles, and erythrocyte membrane-based carriers, highlighting their potential to circumvent the BBB's restrictions. By mimicking native cell properties, these nanocarriers emerge as a promising solution for enhancing drug delivery to the brain, offering a strategic advantage in overcoming the barrier's selective permeability. The unique benefits of leveraging cell membranes from various sources is evaluated and advanced technologies for fabricating cell membrane-encapsulated nanoparticles capable of masquerading as endogenous cells are examined. This enables the targeted delivery of a broad spectrum of therapeutic agents, ranging from small molecule drugs to proteins, thereby providing an innovative approach to neurocare. Further, the review contrasts the capabilities and limitations of these biomimetic nanocarriers with traditional delivery methods, underlining their potential to enable targeted, sustained, and minimally invasive treatment modalities. This review is concluded with a perspective on the clinical translation of these biomimetic systems, underscoring their transformative impact on the therapeutic landscape for intractable brain diseases.

2.
Carbohydr Res ; 539: 109107, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38613897

RESUMO

Chemoresistance poses a significant obstacle in the effective treatment of cancer, limiting the success of chemotherapy regimens. N-glycosylation, the most important post-translational modification (PTM), plays multifaceted roles in the intricate landscape of cancer progression, particularly drug resistance in cancer cells. This review explores the complex relationship between N-glycosylation and chemoresistance in cancer. Altered glycosylation patterns have been proven to impact drug efflux mechanisms in cancer cells, which can further influence the intracellular concentration of chemotherapy drugs. Moreover, N-glycosylation also plays a regulatory role in cell signaling pathways and apoptosis regulators, continuously affecting the stemness and survival of cancer cells under the selective pressure of chemotherapy. Additionally, the impact of the tumor microenvironment on glycosylation patterns adds complexity to this interplay. This review discusses current research findings, challenges, and future directions based on the roles of N-glycosylation in cancer chemoresistance, emphasizing the potential for targeted therapeutic interventions to enhance the effectiveness of chemotherapy and improve patient outcomes.


Assuntos
Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Glicosilação , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Animais
3.
IEEE Trans Image Process ; 33: 2238-2251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38470579

RESUMO

Satellite video multi-label scene classification predicts semantic labels of multiple ground contents to describe a given satellite observation video, which plays an important role in applications like ocean observation, smart cities, et al. However, the lack of a high-quality and large-scale dataset prevents further improvement of the task. And existing methods on general videos have the difficulty to represent the local details of ground contents when directly applied to the satellite videos. In this paper, our contributions include (1) we develop the first publicly available and large-scale satellite video multi-label scene classification dataset. It consists of 18 classes of static and dynamic ground contents, 3549 videos, and 141960 frames. (2) we propose a baseline method with the novel Spatial and Temporal Feature Cooperative Encoding (STFCE). It exploits the relations between local spatial and temporal features, and models long-term motion information hidden in inter-frame variations. In this way, it can enhance features of local details and obtain the powerful video-scene-level feature representation, which raises the classification performance effectively. Experimental results show that our proposed STFCE outperforms 13 state-of-the-art methods with a global average precision (GAP) of 0.8106 and the careful fusion and joint learning of the spatial, temporal, and motion features are beneficial to achieve a more robust and accurate model. Moreover, benchmarking results show that the proposed dataset is very challenging and we hope it could promote further development of the satellite video multi-label scene classification task.

4.
ChemSusChem ; : e202301567, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517635

RESUMO

The direct synthesis of cyclic carbonates through oxidative carboxylation of alkenes using CO2 and O2 offers a sustainable and carbon-neutral method for CO2 utilization, which is, however, still a largely unexplored field. Here we develop a single-atom catalyst (SAC) Co-N/O-C as the earth-abundant metal catalyst for the oxidative carboxylation of styrene with CO2 and O2. Remarkably, even using the flue gas as an impure CO2 and O2 source, desired cyclic carbonate could be obtained with moderate productivity, which shows the potential for integrated CO2 capture and conversion, leveraging the high CO2 adsorption capacity of Co-N/O-C. In addition, the catalyst can be reused five times without an obvious decline in activity. Detailed characterizations and theoretical calculations elucidate the crucial role of single Co atoms in activating O2 and CO2, as well as controlling selectivity.

5.
Nat Commun ; 15(1): 2218, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472249

RESUMO

Continuous and effective hydrogen evolution under high current densities remains a challenge for water electrolysis owing to the rapid performance degradation under continuous large-current operation. In this study, theoretical calculations, operando Raman spectroscopy, and CO stripping experiments confirm that Ru nanocrystals have a high resistance against deactivation because of the synergistic adsorption of OH intermediates (OHad) on the Ru and single atoms. Based on this conceptual model, we design the Ni single atoms modifying ultra-small Ru nanoparticle with defect carbon bridging structure (UP-RuNiSAs/C) via a unique unipolar pulse electrodeposition (UPED) strategy. As a result, the UP-RuNiSAs/C is found capable of running steadily for 100 h at 3 A cm-2, and shows a low overpotential of 9 mV at a current density of 10 mA cm-2 under alkaline conditions. Moreover, the UP-RuNiSAs/C allows an anion exchange membrane (AEM) electrolyzer to operate stably at 1.95 Vcell for 250 h at 1 A cm-2.

6.
Int J Biol Macromol ; 264(Pt 1): 130543, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432271

RESUMO

Hydrogel microbeads can be used to enhance the stability of probiotics during gastrointestinal delivery and storage. In this study, the pectin-alginate hydrogel was enhanced by adding montmorillonite filler to produce microbeads for encapsulating Lactobacillus kefiranofaciens (LK). Results showed that the viscosity of biopolymer solutions with 1 % (PAMT1) and 3 % (PAMT3) montmorillonite addition was suitable for producing regular-shaped microbeads. A layered cross-linked network was formed on the surface of PAMT3 microbeads through electrostatic interaction between pectin-alginate and montmorillonite filler, and the surrounding LK with adsorbed montmorillonite was encapsulated inside the microbeads. PAMT3 microbeads reduced the loss of viability of LK when passing through the gastric acid environment, and facilitated the slow release of LK in the intestine and colonic colonization. The maximum decrease in viability among all filler groups was 1.21 log CFU/g after two weeks of storage, while PAMT3 freeze-drying microbeads only decreased by 0.46 log CFU/g, indicating that the gel layer synergized with the adsorbed layer to provide dual protection for probiotics. Therefore, filler-reinforced microbeads are a promising bulk encapsulation carrier with great potential for the protection and delivery of probiotics and can be developed as food additives for dairy products.


Assuntos
Alginatos , Lactobacillus , Probióticos , Pectinas , Bentonita , Microesferas , Hidrogéis , Viabilidade Microbiana
7.
J Am Chem Soc ; 146(9): 6037-6044, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38377954

RESUMO

Alkene hydroformylation is one of the largest industrial reactions on an industrial scale; however, the development of nonnoble heterogeneous catalysts is usually limited by their low activities and stabilities. Herein, we constructed a 1% Co2C/SiO2 catalyst featuring Co-Cvacancy-Co-C symmetry-breaking sites, which generated a polar surface exhibiting a moderate charge density gradient at the localized Co atoms. Comparatively, this catalyst exhibited notable enhancements in the adsorption and activation of the reactants, as well as in the polarity between intermediates. Significantly, the spatial distance between the adsorption sites of intermediates was reduced, thereby effectively decreasing the energy barrier of reaction processes. As the density of the symmetry-breaking sites increased, the turnover number for propene hydroformylation soared to 18 363, exceeding the activity of heterogeneous Co-based catalysts reported thus far by 1 or 2 orders of magnitude, and the catalyst exhibited high stability during the reaction. This study provides a methodology for constructing atomically active sites, which holds great potential for the design and development of highly efficient catalysts.

8.
Plant Cell Environ ; 47(5): 1797-1812, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38314665

RESUMO

As the most abundant form of methylation modification in messenger RNA (mRNA), the distribution of N6-methyladenosine (m6A) has been preliminarily revealed in herbaceous plants under salt stress, but its function and mechanism in woody plants were still unknown. Here, we showed that global m6A levels increased during poplar response to salt stress. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that m6A significantly enriched in the coding sequence region and 3'-untranslated regions in poplar, by recognising the conserved motifs, AGACU, GGACA and UGUAG. A large number of differential m6A transcripts have been identified, and some have been proved involving in salt response and plant growth and development. Further combined analysis of MeRIP-seq and RNA-seq revealed that the m6A hypermethylated and enrich in the CDS region preferred to positively regulate expression abundance. Writer inhibitor, 3-deazaneplanocin A treatment increased the sensitivity of poplar to salt stress by reducing mRNA stability to regulate the expression of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Furthermore, we verified that the methyltransferase PagFIP37 plays a positively role in the response of poplar to salt stress, overexpressed lines have stronger salt tolerance, while RNAi lines were more sensitive to salt, which relied on regulating mRNA stability in an m6A manner of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Collectively, these results revealed the regulatory role of m6A methylation in poplar response to salt stress, and revealed the importance and mechanism of m6A methylation in the response of woody plants to salt stress for the first time.


Assuntos
Adenosina/análogos & derivados , Populus , Metilação de RNA , Estresse Salino/genética , Metiltransferases/genética , Populus/genética , RNA Mensageiro/genética
9.
J Control Release ; 368: 208-218, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395156

RESUMO

B cell-targeted cancer vaccines are receiving increasing attention in immunotherapy due to the combined antibody-secreting and antigen-presenting functions. In this study, we propose a natural IgM-hitchhiking delivery strategy to co-deliver tumor antigens and adjuvants to splenic marginal zone B (MZB) cells. We constructed nanovaccines (FA-sLip/OVA/MPLA) consisting of classical folic acid (FA)-conjugated liposomes co-loaded with ovalbumin (OVA) and toll-like receptor 4 agonists, MPLA. We found that natural IgM absorption could be manipulated at the bio-nano interface on FA-sLip/OVA/MPLA, enabling targeted delivery to splenic MZB cells. Systemic administration of FA-sLip/OVA/MPLA effectively activated splenic MZB cells via IgM-mediated multiplex pathways, eliciting antigen-specific humoral and cytotoxic T lymphocyte responses, and ultimately retarding E.G7-OVA tumor growth. In addition, combining FA-sLip/OVA/MPLA immunization with anti-PD-1 treatments showed improved antitumor efficiency. Overall, this natural IgM-hitchhiking delivery strategy holds great promise for efficient, splenic MZB cell-targeted delivery of cancer vaccines in future applications.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Animais , Camundongos , Nanovacinas , Neoplasias/terapia , Antígenos de Neoplasias , Ovalbumina , Imunoglobulina M , Camundongos Endogâmicos C57BL
10.
JMIR Med Inform ; 12: e49138, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38297829

RESUMO

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

11.
Planta ; 259(3): 66, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332379

RESUMO

MAIN CONCLUSION: Optimal levels of indole-3-butyric acid (IBA) applied at the stem base promote adventitious root (AR) initiation and primordia formation, thus promoting the rooting of leafy micro-cuttings of tetraploid Robinia pseudoacacia. Tetraploid Robinia pseudoacacia L. is a widely cultivated tree in most regions of China that has a hard-rooting capability, propagated by stem cuttings. This study utilizes histological, physiological, and transcriptomic approaches to explore how root primordia are induced after indole butyric acid (IBA) treatment of micro-cuttings. IBA application promoted cell divisions in some cells within the vasculature, showing subcellular features associated with adventitious root (AR) founder cells. The anatomical structure explicitly showed that AR initiated from the cambium layer and instigate the inducible development of AR primordia. Meanwhile, the hormone data showed that similar to that of indole-3-acetic acid, the contents of trans-zeatin and abscisic acid peaked at early stages of AR formation and increased gradually in primordia formation across the subsequent stages, suggesting their indispensable roles in AR induction. On the contrary, 24-epibrassinolide roughly maintained at extremely high levels during primordium initiation thoroughly, indicating its presence was involved in cell-specific reorganization during AR development. Furthermore, antioxidant activities transiently increased in the basal region of micro-cuttings and may serve as biochemical indicators for distinct rooting phases, potentially aiding in AR formation. Transcriptomic analysis during the early stages of root formation shows significant downregulation of the abscisic acid and jasmonate signaling pathways, while ethylene and cytokinin signaling seems upregulated. Network analysis of genes involved in carbon metabolism and photosynthesis indicates that the basal region of the micro-cuttings undergoes rapid reprogramming, which results in the breakdown of sugars into pyruvate. This pyruvate is then utilized to fuel the tricarboxylic acid cycle, thereby sustaining growth through aerobic respiration. Collectively, our findings provide a time-course morphophysiological dissection and also suggest the regulatory role of a conserved auxin module in AR development in these species.


Assuntos
Ácido Abscísico , Robinia , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Robinia/genética , Tetraploidia , Ácidos Indolacéticos/metabolismo , Perfilação da Expressão Gênica , Piruvatos/metabolismo , Raízes de Plantas/metabolismo
12.
Cancer Sci ; 115(4): 1196-1208, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38288901

RESUMO

Fms-like tyrosine kinase-3 (FLT3) is a commonly mutated gene in acute myeloid leukemia (AML). The two most common mutations are the internal-tandem duplication domain (ITD) mutation and the tyrosine kinase domain (TKD) mutation. FLT3-ITD and FLT3-TKD exhibit distinct protein stability, cellular localization, and intracellular signaling. To understand the underlying mechanisms, we performed proximity labeling with TurboID to identify proteins that regulate FLT3-ITD or -TKD differently. We found that BRCA1/BRCA2-containing complex subunit 36 (BRCC36), a specific K63-linked polyubiquitin deubiquitinase, was exclusively associated with ITD, not the wild type of FLT3 and TKD. Knockdown of BRCC36 resulted in decreased signal transducers and activators of transcription 5 phosphorylation and cell proliferation in ITD cells. Consistently, treatment with thiolutin, an inhibitor of BRCC36, specifically suppressed cell proliferation and induced cell apoptosis in ITD cells. Thiolutin efficiently affected leukemia cell lines expressing FLT3-ITD cell viability and exhibited mutual synergies with quizartinib, a standard clinical medicine for AML. Furthermore, mutation of the lysine at 609 of ITD led to significant suppression of K63 polyubiquitination and decreased its stability, suggesting that K609 is a critical site for K63 ubiquitination specifically recognized by BRCC36. These data indicate that BRCC36 is a specific regulator for FLT3-ITD, which may shed light on developing a novel therapeutic approach for AML.


Assuntos
Leucemia Mieloide Aguda , Tirosina Quinase 3 Semelhante a fms , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Transdução de Sinais/fisiologia , Mutação , Estabilidade Proteica
13.
ACS Nano ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38266247

RESUMO

Overproduction of reactive oxygen species by damaged mitochondria after ischemia is a key factor in the subsequent cascade of damage. Delivery of therapeutic agents to the mitochondria of damaged neurons in the brain is a potentially promising targeted therapeutic strategy for the treatment of ischemic stroke. In this study, we developed a ceria nanoenzymes synergistic drug-carrying nanosystem targeting mitochondria to address multiple factors of ischemic stroke. Each component of this nanosystem works individually as well as synergistically, resulting in a comprehensive therapy. Alleviation of oxidative stress and modulation of the mitochondrial microenvironment into a favorable state for ischemic tolerance are combined to restore the ischemic microenvironment by bridging mitochondrial and multiple injuries. This work also revealed the detailed mechanisms by which the proposed nanodelivery system protects the brain, which represents a paradigm shift in ischemic stroke treatment.

14.
Int J Mol Sci ; 25(2)2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38279314

RESUMO

Polyploid breeding techniques aid in the cultivation of new forestry cultivars, thus expanding the suite of strategies for the improvement of arboreal traits and innovation within the field of forestry. Compared to diploid Robinia pseudoacacia L. (black locust) 'D26-5①' (2×), its dwarfed homologous tetraploid 'D26-5②' (4×) variety has better application prospects in garden vegetation guardrails and urban landscape. However, the molecular mechanism of the generation and growth of this dwarf variety is still unclear. Here, plant growth and development as well as histological differences between the diploid and its autotetraploid were investigated. Levels of endogenous hormones at three different developmental stages (20, 40, and 70 days) of 2× and homologous 4× tissue culture plantlets were assessed, and it was found that the brassinosteroid (BR) contents of the former were significantly higher than the latter. Transcriptome sequencing data analysis of 2× and homologous 4× showed that differentially expressed genes (DEGs) were significantly enriched in plant hormone synthesis and signal transduction, sugar and starch metabolism, and the plant circadian rhythm pathway, which are closely related to plant growth and development. Therefore, these biological pathways may be important regulatory pathways leading to dwarfism and slow growth in tetraploids. Additionally, utilizing weighted gene coexpression network analysis (WGCNA), we identified three crucial differentially expressed genes (DEGs)-PRR5, CYP450, and SPA1-that potentially underlie the observed ploidy variation. This study provides a new reference for the molecular mechanism of dwarfism in dwarfed autotetraploid black locusts. Collectively, our results of metabolite analysis and comparative transcriptomics confirm that plant hormone signaling and the circadian rhythm pathway result in dwarfism in black locusts.


Assuntos
Nanismo , Robinia , Transcriptoma , Tetraploidia , Robinia/genética , Reguladores de Crescimento de Plantas/metabolismo , Melhoramento Vegetal , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas
15.
J Pediatr (Rio J) ; 100(2): 156-162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37837994

RESUMO

OBJECTIVE: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. METHODS: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. RESULTS: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. CONCLUSION: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.


Assuntos
Artrite Infecciosa , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Sepse , Infecções Estafilocócicas , Lactente , Recém-Nascido , Humanos , Masculino , Feminino , Estudos Retrospectivos , Artrite Infecciosa/complicações , Artrite Infecciosa/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus , Osteomielite/complicações , Osteomielite/tratamento farmacológico , Sepse/complicações , Antibacterianos/uso terapêutico
16.
J Biol Chem ; 300(1): 105513, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38042483

RESUMO

α1,6-Fucosyltransferase (Fut8) catalyzes the transfer of fucose to the innermost GlcNAc residue of N-glycan to form core fucosylation. Our previous studies showed that lipopolysaccharide (LPS) treatment highly induced neuroinflammation in Fut8 homozygous KO (Fut8-/-) or heterozygous KO (Fut8+/-) mice, compared with the WT (Fut8+/+) mice. To understand the underlying mechanism, we utilized a sensitive inflammation-monitoring mouse system that contains the human interleukin-6 (hIL6) bacterial artificial chromosome transgene modified with luciferase (Luc) reporter cassette. We successfully detected LPS-induced neuroinflammation in the central nervous system by exploiting this bacterial artificial chromosome transgenic monitoring system. Then we examined the effects of l-fucose on neuroinflammation in the Fut8+/- mice. The lectin blot and mass spectrometry analysis showed that l-fucose preadministration increased the core fucosylation levels in the Fut8+/- mice. Notably, exogenous l-fucose attenuated the LPS-induced IL-6 mRNA and Luc mRNA expression in the cerebral tissues, confirmed using the hIL6-Luc bioluminescence imaging system. The activation of microglial cells, which provoke neuroinflammatory responses upon LPS stimulation, was inhibited by l-fucose preadministration. l-Fucose also suppressed the downstream intracellular signaling of IL-6, such as the phosphorylation levels of JAK2 (Janus kinase 2), Akt (protein kinase B), and STAT3 (signal transducer and activator of transcription 3). l-Fucose administration increased gp130 core fucosylation levels and decreased the association of gp130 with the IL-6 receptor in Fut8+/- mice, which was further confirmed in BV-2 cells. These results indicate that l-fucose administration ameliorates the LPS-induced neuroinflammation in the Fut8+/- mice, suggesting that core fucosylation plays a vital role in anti-inflammation and that l-fucose is a potential prophylactic compound against neuroinflammation.


Assuntos
Fucose , Inflamação , Lipopolissacarídeos , Animais , Humanos , Camundongos , Receptor gp130 de Citocina , Fucose/farmacologia , Fucose/metabolismo , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Doenças Neuroinflamatórias , RNA Mensageiro
17.
J Exp Bot ; 75(3): 733-745, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-37930766

RESUMO

Reversal of plant developmental status from the mature to the juvenile phase, thus leading to the restoration of the developmental potential, is referred to as plant rejuvenation. It involves multilayer regulation, including resetting gene expression patterns, chromatin remodeling, and histone modifications, eventually resulting in the restoration of juvenile characteristics. Although plants can be successfully rejuvenated using some forestry practices to restore juvenile morphology, physiology, and reproductive capabilities, studies on the epigenetic mechanisms underlying this process are in the nascent stage. This review provides an overview of the plant rejuvenation process and discusses the key epigenetic mechanisms involved in DNA methylation, histone modification, and chromatin remodeling in the process of rejuvenation, as well as the roles of small RNAs in this process. Additionally, we present new inquiries regarding the epigenetic regulation of plant rejuvenation, aiming to advance our understanding of rejuvenation in sexually and asexually propagated plants. Overall, we highlight the importance of epigenetic mechanisms in the regulation of plant rejuvenation, providing valuable insights into the complexity of this process.


Assuntos
Epigênese Genética , Memória Epigenética , Rejuvenescimento , Plantas/metabolismo , Metilação de DNA , Regulação da Expressão Gênica de Plantas
19.
Food Chem ; 440: 138244, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142554

RESUMO

Flusilazole is a triazole fungicide with residues that are potentially toxic to humans. It enters the human body mainly through food, although its bactericidal activity is substantial. In this study, an electrochemical sensor Fe/Fe2O3@C with a core-shell structure was constructed to efficiently detect flusilazole by annealing MIL-53(Fe) which was prepared by a simple solvothermal method. Transmission electron microscopy and scanning electron microscopy were used to characterize the apparent morphology of MIL-53(Fe) and Fe/Fe2O3@C, and their structures were further characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, powder X-ray diffraction, and the mapping of elements by energy dispersive spectroscopy. The electrochemical behavior of Fe/Fe2O3@C in the detection of flusilazole was evaluated by differential pulse voltammetry under optimal conditions. The results of the study indicate that the Fe/Fe2O3@C electrochemical sensor displayed excellent detection capabilities for flusilazole, where the sensor exhibited a wide detection range from 1.00 × 10-4 to 1.00 × 10-12 mol/L with an incredibly low LOD of 593 fM, making it highly sensitive to trace amounts of flusilazole. Moreover, Fe/Fe2O3@C demonstrated superior reproducibility, stability, and resistance to interference, highlighting its reliability in practical applications. The sensor was also successfully utilized to quantitatively detect flusilazole in various real samples, which suggests that Fe/Fe2O3@C has broad-spectrum environmental resistance and can effectively and rapidly detect flusilazole residues in different types of food items and environmental matrices. The study also delved into the mechanism of Fe/Fe2O3@C for the detection of flusilazole, providing a deeper understanding of the functionality of this sensor. Overall, these findings emphasize the practical significance of Fe/Fe2O3@C as an electrochemical sensor, showcasing its potential for real-world applications in food safety and environmental monitoring.


Assuntos
Inocuidade dos Alimentos , Silanos , Triazóis , Humanos , Reprodutibilidade dos Testes , Microscopia Eletrônica de Varredura , Técnicas Eletroquímicas/métodos
20.
BMC Cardiovasc Disord ; 23(1): 612, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093240

RESUMO

BACKGROUND: There are sex differences in many risk factors associated with coronary artery disease (CAD). CT-derived fractional flow reserve (CT-FFR) and fat attenuation index (FAI) have been shown to independently predict cardiovascular events. We aimed to examine the impact of sex on the prognostic value of CT-FFR and FAI in suspected CAD patients, and to examine the incremental prognostic value of FAI over CT-FFR in both sex. METHODS: A total of 1334 consecutive suspected CAD subjects who underwent coronary computed tomographic angiography (CCTA) were retrospectively collected. We divided the patients into males and females and calculated CT-FFR and FAI data from CCTA images. Kaplan-Meier analysis was used to assess the risk of major adverse cardiovascular events (MACE) stratified by CT-FFR and FAI in both sex. Cox regression models were used to assess the incremental prognostic value of FAI by adding the variable to a model that included CT-FFR and clinical variables. RESULTS: During a median follow-up of 2.08 years, 212 patients had MACE. CT-FFR ≤ 0.80 was significantly associated with MACE in both sex. FAI value of left anterior descending artery (FAI[LAD]) and FAI value of left circumflex (FAI[LCX]) ≥ 70.1 were significantly associated with MACE in females. FAI[LCX] added incremental prognostic value over clinical and CT-FFR variables in females, with hazard ratio (HR) 3.230 (1.982-5.265, P = 0.000), Harrel's C 0.669 (P < 0.001), net reclassification improvement (NRI) 0.161 (0.073-0.260, P < 0.001), and integrated discrimination index (IDI) 0.036 (0.008-0.090, P = 0.010). FAI[LAD] did not enhance risk prediction in females (Harrel's C 0.643, P = 0.054; NRI 0.041, P = 0.189; IDI 0.005, P = 0.259). The decision curve analysis demonstrated that the model including FAI[LCX] resulted in the highest net benefit. CONCLUSIONS: In suspected CAD patients, the prognostic value of CT-FFR is not significantly biased by sex. The prognostic value of FAI[LAD] and FAI[LCX] were significantly associated with MACE in females, but not males. FAI[LCX], not FAI[LAD], added incremental prognostic value over CT-FFR and might enhance CT-FFR risk stratification in females.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Humanos , Masculino , Feminino , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária/métodos , Estudos Retrospectivos , Prognóstico , Tomografia Computadorizada por Raios X , Angiografia por Tomografia Computadorizada/métodos , Valor Preditivo dos Testes
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