Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.259
Filtrar
1.
New Phytol ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39091140

RESUMEN

Chloroplasts play a crucial role in plant defense against pathogens, making them primary targets for pathogen effectors that suppress host immunity. This study characterizes the Plasmopara viticola CRN-like effector, PvCRN20, which interacts with DEG5 in the cytoplasm but not with its interacting protein, DEG8, which is located in the chloroplast. By transiently overexpressing in tobacco leaves, we show that PvCRN20 could inhibit INF1- and Bax-triggered cell death. Constitutive expression of PvCRN20 suppresses the accumulation of reactive oxygen species (ROS) and promotes pathogen colonization. PvCRN20 reduces DEG5 entry into chloroplasts, thereby disrupting DEG5 and DEG8 interactions in chloroplasts. Overexpression of VvDEG5 and VvDEG8 induces ROS accumulation and enhances grapevine resistance to P. viticola, whereas knockout of VvDEG8 represses ROS production and promotes P. viticola colonization. Consistently, ectopic expression of VvDEG5 and VvDEG8 in tobacco promotes chloroplast-derived ROS accumulation, whereas co-expression of PvCRN20 counteracted this promotion by VvDEG5. Therefore, DEG5 is essential for the virulence function of PvCRN20. Although PvCRN20 is located in both the nucleus and cytoplasm, only cytoplasmic PvCRN20 suppresses plant immunity and promotes pathogen infection. Our results reveal that PvCRN20 dampens plant defenses by repressing the chloroplast import of DEG5, thus reducing host ROS accumulation and facilitating pathogen colonization.

2.
Leukemia ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095502

RESUMEN

Residual normal plasma cells (NPCs), which compete with tumor plasma cells, play an important role in multiple myeloma. However, large-scale cohort studies investigating residual NPCs, especially at the minimal residual disease (MRD) phase, are currently lacking. In this study, we conducted a comprehensive investigation into the clinical significance of residual NPCs throughout the entire disease course in 1363 myeloma patients from the NICHE cohort (NCT04645199). Our results revealed that myeloma patients with high baseline NPCs ratio (≥5%) exhibited distinct indolent features, characterized by lower tumor burden, reduced frequencies of cytopenia, immunoparesis, and high-risk cytogenetics. Importantly, high residual NPCs ratio at diagnosis or relapse was independently associated with favorable survival. High absolute percentages of NPCs at undetectable MRD were related with superior clinical benefit and immune reconstitution. At MRD-positive phases, grouping based on NPCs ratio (<50%, 50-90%, ≥90%) demonstrated better risk stratification compared to residual tumor log levels. Based on the time-dependent NPCs ratio trend, we developed a dynamic MRD model that classifies patients into three groups with diverse longitudinal trends, leading to distinct prognoses. Collectively, residual NPCs serves not only as a valuable complementary biomarker for risk stratification but also provides valuable insights on reclassifications and kinetics of MRD.

3.
Immun Inflamm Dis ; 12(8): e1361, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39092772

RESUMEN

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17ß-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms. METHODS: Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining. RESULTS: The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown. CONCLUSION: E2 promoted the progression of TMJOA.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Estradiol , Osteoartritis , Animales , Ratas , Estradiol/farmacología , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/genética , Progresión de la Enfermedad , Sinoviocitos/metabolismo , Sinoviocitos/efectos de los fármacos , Sinoviocitos/patología , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Articulación Temporomandibular/patología , Articulación Temporomandibular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Células Cultivadas , Masculino , Adenosina/metabolismo , Adenosina/análogos & derivados , Proliferación Celular/efectos de los fármacos
4.
Int J Biol Macromol ; : 134378, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39097048

RESUMEN

The soy hull polysaccharide (SHP) exhibits excellent interfacial activity and holds potential as an emulsifier for emulsions. To reveal the behavior of SHP at the water/oil (W/O) interface in situ, molecular dynamics (MD) simulations and particle tracking microrheology were used in this study. The results of MD reveal that SHP molecular spontaneously move toward the interface and rhamnogalacturonan-I initiates this movement, while its galacturonic acids on it act as anchors to immobilize the SHP molecules at the W/O interface. Microrheology results suggest that SHP forms microgels at the W/O interface, with the lattices of the microgels continually undergoing dynamic changes. At low concentrations of SHP and short interfacial formation time, the network of the microgels is weak and dominated by viscous properties. However, when SHP reaches 0.75 % and the interfacial formation time is about 60 min, the microgels show perfect elasticity, which is beneficial for stabilizing emulsions.

5.
Dalton Trans ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39049578

RESUMEN

The design of efficient catalysts for photocatalytic CO2 conversion is of great importance for the sustainable development of society. Herein, three polyoxometalate (POM)-based crystalline materials were formulated prepared by substituting transition metals and adjusting solvent acidity with 2-(2-pyridyl) benzimidazole (pyim) as the light-trapping ligand, namely {[SiW12O40][Co(pyim)2]2}·2C2H5OH (SiW12Co2), {[SiW12O40][Ni(pyim)2]2}·2C2H5OH (SiW12Ni2), and {[SiW12O40][Mn(pyim)2]2}·2C2H5OH (SiW12Mn2). X-ray crystallography diffraction analysis indicates that the three complexes exhibit isostructural properties, and form a stable one-dimensional chain structure stabilized by two [M(pyim)2]22+ (M = Co, Ni, and Mn) fragments serving as dual-nodes to the adjacent SiW12 units. A comprehensive analysis of the structural characterization and photocatalytic CO2 reduction properties is presented. Under light irradiation, SiW12Co2 exhibited a remarkable CO generation rate of 10 733 µmol g-1 h-1 with a turnover number of 328, outperforming most of the reported heterogeneous POM-based photocatalysts. Besides, cycling tests revealed that SiW12Co2 is an efficient and stable photocatalyst with great recyclability for at least four successive runs. This study proves that the successful incorporation of diverse transition metals into the POM anion could facilitate the development of highly efficient photocatalysts for the CO2RR.

6.
Arch Pharm Res ; 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39060657

RESUMEN

SMARCA5, a protein in the SWI/SNF family, has been previously implicated in the development of ulcerative colitis (UC) through methylation. However, the specific molecular mechanisms by which SMARCA5 contributes to colonic inflammation and the imbalance between Th17 and Treg cells remain unclear. This study was designed to explore these molecular mechanisms. A UC mouse model was established using dextran sulfate sodium induction, followed by measurements of mouse weight, disease activity index (DAI) score, colon length, pathological changes in the colon, and FITC-dextran concentration. The levels of IL-17a, IFN-γ, IL-6, TNF-α, TGF-ß, and IL-10 were measured, along with the protein expression of ZO-1 and Occludin. Flow cytometry was used to assess the presence of IL-17 + CD4 + (Th17 +) cells and FOXP3 + CD25 + CD4 + (Treg +) cells in the spleen and mesenteric lymph nodes of UC mice. We observed that SMARCA5 and RNF180 were increased, while ALKBH5 was downregulated in UC mouse colon tissue. SMARCA5 or RNF180 knockdown or ALKBH5 overexpression ameliorated the colon inflammation and Th17/Treg cell imbalance in UC mice, shown by increased body weight, colon length, FOXP3 + CD25 + CD4 + T cells, and the levels of ZO-1, Occludin, TGF-ß, IL-10, and FOXP3. It decreased DAI scores, IL-17 + CD4 + T cells, and levels of IL-17a, IFN-γ, IL-6, TNF-α, and ROR-γt. ALKBH5 inhibited SMARCA5 expression via m6A modification, while RNF180 reduced ALKBH5 expression via ubiquitination. Our findings indicate that RNF180 aggravated the colon inflammation and Th17/Treg cell imbalance in UC mice by regulating the ALKBH5/SMARCA5 axis.

7.
Exp Dermatol ; 33(7): e15133, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39045898

RESUMEN

The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well-defined molecular mechanism governing hypertrophic scarring has led to less-than-ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF-ß/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL-1 and COL-3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF-ß1/Smad3 pathway by suppressing TGF-ß1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen-based extracellular matrix and fibrosis through the TGF-ß1/Smad3 pathway.


Asunto(s)
Cicatriz Hipertrófica , Decorina , Proteína smad3 , Factor de Crecimiento Transformador beta , Decorina/genética , Decorina/metabolismo , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal , Técnicas de Silenciamiento del Gen , Humanos , Proteína smad3/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Matriz Extracelular/metabolismo , Proliferación Celular , Movimiento Celular
8.
J Environ Manage ; 366: 121883, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39047437

RESUMEN

Ozone pollution is the focus of current environmental governance in China and high-quality prediction of ozone concentration is the prerequisite to effective policymaking. The studied ozone pollution time series exhibits distinct seasonality and secular trends and is associated with various factors. This study developed an interpretable hybrid model by combining STL decomposition and the Transformer (STL-Transformer) with the prior information of ozone time series and global multi-source information as prediction basis. The STL decomposition decomposes ozone time series into trend, seasonal, and remainder components. Then, the three components, along with other air quality and meteorological data, are integrated into the input sequence of the Transformer. The experiment results show that the STL-Transformer outperforms the other five state-of-the-art models, including the standard Transformer. Specially, the univariate forecasting for ozone relies on mimicking the patterns and trends that have occurred in the past. In contrast, multivariate forecasting can effectively capture complex relationships and dependencies involving multiple variables. The method successfully grasps the prior and global multi-source information and simultaneously improves the interpretability of ozone prediction with high precision. This study provides new insights for air pollution forecasting and has reliable theoretical value and practical significance for environmental governance.

9.
Environ Res ; 260: 119658, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39053756

RESUMEN

Surface ozone (O3) poses a significant threat to urban vegetation health, and assessing the O3 risk across woody species is of vital importance for maintaining the health of urban infrastructure. In the present study, Jarvis-type stomatal conductance model was parameterized for ten urban species in northern China. Incorporating the effects of time of day and diurnal O3 concentration significantly enhanced the model performance. For different plant functional types (greening trees, greening shrubs, and orchard-grown trees), three parameterizations were established to estimate stomatal O3 uptake (POD1, phytotoxic O3 dose over an hourly threshold of 1 nmol m-2 s-1). The differences in POD1 between greening trees and shrubs were primarily due to the difference in their stomatal sensitivity to light. Orchard-grown trees displayed the lowest O3 removal capacity (lowest value of POD1) because of their shorter growing season despite of high stomatal conductance. These results indicated that plant phenology and light responsiveness determined stomatal O3 uptake, and the three parameterizations developed here could be applicable to various urban species in northern regions. Among climatic factors for O3 risk assessment, O3 concentration was the most important factor determining annual variation of POD1, which was primarily driven by air temperature. However, when O3 pollution decreased, O3 concentration exhibited less dependence on temperature and more dependence on light. These findings provide crucial insights for urban policy-makers and environmental scientists aiming to mitigate O3 pollution effects and enhance urban vegetation health.

10.
Ecotoxicol Environ Saf ; 282: 116703, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38986335

RESUMEN

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage.

11.
Biotechnol J ; 19(7): e2400115, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38987223

RESUMEN

The nonconventional methylotrophic yeast Komagataella phaffii is widely applied in the production of industrial enzymes, pharmaceutical proteins, and various high-value chemicals. The development of robust and versatile genome editing tools for K. phaffii is crucial for the design of increasingly advanced cell factories. Here, we first developed a base editing method for K. phaffii based on the CRISPR-nCas9 system. We engineered 24 different base editor constructs, using a variety of promoters and cytidine deaminases (CDAs). The optimal base editor (PAOX2*-KpA3A-nCas9-KpUGI-DAS1TT) comprised a truncated AOX2 promoter (PAOX2*), a K. phaffii codon-optimized human APOBEC3A CDA (KpA3A), human codon-optimized nCas9 (D10A), and a K. phaffii codon-optimized uracil glycosylase inhibitor (KpUGI). This optimal base editor efficiently performed C-to-T editing in K. phaffii, with single-, double-, and triple-locus editing efficiencies of up to 96.0%, 65.0%, and 5.0%, respectively, within a 7-nucleotide window from C-18 to C-12. To expand the targetable genomic region, we also replaced nCas9 in the optimal base editor with nSpG and nSpRy, and achieved 50.0%-60.0% C-to-T editing efficiency for NGN-protospacer adjacent motif (PAM) sites and 20.0%-93.2% C-to-T editing efficiency for NRN-PAM sites, respectively. Therefore, these constructed base editors have emerged as powerful tools for gene function research, metabolic engineering, genetic improvement, and functional genomics research in K. phaffii.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Saccharomycetales , Edición Génica/métodos , Saccharomycetales/genética , Sistemas CRISPR-Cas/genética , Humanos , Citidina Desaminasa/genética , Citidina Desaminasa/metabolismo , Regiones Promotoras Genéticas/genética , Proteínas
12.
J Med Virol ; 96(7): e29795, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39007429

RESUMEN

Despite increased risk of severe acute respiratory syndrome coronavirus 2 infections and higher rates of COVID-19-related complications, racialized and Indigenous communities in Canada have lower immunization uptake compared to White individuals. However, there is woeful lack of data on predictors of COVID-19 vaccine mistrust (VM) that accounts for diverse social and cultural contexts within specific racialized and Indigenous communities. Therefore, we sought to characterize COVID-19 VM among Arab, Asian, Black, and Indigenous communities in Canada. An online survey was administered to a nationally representative, ethnically diverse panel of participants in October 2023. Arabic, Asian, Indigenous, and Black respondents were enriched in the sampling panel. Data were collected on demographics, COVID-19 VM, experience of racial discrimination, health literacy, and conspiracy beliefs. We used descriptive and regression analyses to determine the extent and predictors of COVID-19 VM among racialized and Indigenous individuals. All racialized respondents had higher VM score compared to White participants. Among 4220 respondents, we observed highest VM among Black individuals (12.18; ±4.24), followed by Arabic (12.12; ±4.60), Indigenous (11.84; ±5.18), Asian (10.61; ±4.28), and White (9.58; ±5.00) participants. In the hierarchical linear regression analyses, Black participants, women, everyday racial discrimination, and major experience of discrimination were positively associated with COVID-19 VM. Effects of racial discrimination were mediated by addition of conspiracy beliefs to the model. Racialized and Indigenous communities experience varying levels of COVID-19 VM and carry specific predictors and mediators to development of VM. This underscores the intricate interaction between race, gender, discrimination, and VM that need to be considered in future vaccination campaigns.


Asunto(s)
Árabes , Vacunas contra la COVID-19 , COVID-19 , Alfabetización en Salud , Pueblos Indígenas , Racismo , Humanos , Femenino , Masculino , Adulto , COVID-19/prevención & control , COVID-19/etnología , Canadá/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Persona de Mediana Edad , Pueblos Indígenas/estadística & datos numéricos , Confianza , Adulto Joven , Encuestas y Cuestionarios , Conocimientos, Actitudes y Práctica en Salud , Anciano , Pueblo Asiatico , Población Negra/estadística & datos numéricos , Población Negra/psicología , SARS-CoV-2/inmunología , Vacunación/psicología , Vacunación/estadística & datos numéricos , Adolescente , Etnicidad
13.
Theranostics ; 14(10): 3927-3944, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38994017

RESUMEN

Rationale: Myocardial infarction (MI) is a severe global clinical condition with widespread prevalence. The adult mammalian heart's limited capacity to generate new cardiomyocytes (CMs) in response to injury remains a primary obstacle in developing effective therapies. Current approaches focus on inducing the proliferation of existing CMs through cell-cycle reentry. However, this method primarily elevates cyclin dependent kinase 6 (CDK6) and DNA content, lacking proper cytokinesis and resulting in the formation of dysfunctional binucleated CMs. Cytokinesis is dependent on ribosome biogenesis (Ribo-bio), a crucial process modulated by nucleolin (Ncl). Our objective was to identify a novel approach that promotes both DNA synthesis and cytokinesis. Methods: Various techniques, including RNA/protein-sequencing analysis, Ribo-Halo, Ribo-disome, flow cytometry, and cardiac-specific tumor-suppressor retinoblastoma-1 (Rb1) knockout mice, were employed to assess the series signaling of proliferation/cell-cycle reentry and Ribo-bio/cytokinesis. Echocardiography, confocal imaging, and histology were utilized to evaluate cardiac function. Results: Analysis revealed significantly elevated levels of Rb1, bur decreased levels of circASXL1 in the hearts of MI mice compared to control mice. Deletion of Rb1 induces solely cell-cycle reentry, while augmenting the Ribo-bio modulator Ncl leads to cytokinesis. Mechanically, bioinformatics and the loss/gain studies uncovered that circASXL1/CDK6/Rb1 regulates cell-cycle reentry. Moreover, Ribo-Halo, Ribo-disome and circRNA pull-down assays demonstrated that circASXL1 promotes cytokinesis through Ncl/Ribo-bio. Importantly, exosomes derived from umbilical cord mesenchymal stem cells (UMSC-Exo) had the ability to enhance cardiac function by facilitating the coordinated signaling of cell-cycle reentry and Ribo-bio/cytokinesis. These effects were attenuated by silencing circASXL1 in UMSC-Exo. Conclusion: The series signaling of circASXL1/CDK6/Rb1/cell-cycle reentry and circASXL1/Ncl/Ribo-bio/cytokinesis plays a crucial role in cardiac repair. UMSC-Exo effectively repairs infarcted myocardium by stimulating CM cell-cycle reentry and cytokinesis in a circASXL1-dependent manner. This study provides innovative therapeutic strategies targeting the circASXL1 signaling network for MI and offering potential avenues for enhanced cardiac repair.


Asunto(s)
Ciclo Celular , Citocinesis , Ratones Noqueados , Infarto del Miocardio , Miocitos Cardíacos , Ribosomas , Animales , Ratones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismo , Ribosomas/metabolismo , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Nucleolina , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteína de Retinoblastoma/metabolismo , Proteína de Retinoblastoma/genética , Proliferación Celular , Masculino , Humanos
14.
World J Gastrointest Oncol ; 16(6): 2757-2768, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38994162

RESUMEN

BACKGROUND: Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. AIM: To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. METHODS: High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. RESULTS: Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. CONCLUSION: Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

15.
Molecules ; 29(13)2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38998929

RESUMEN

Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.

16.
Front Endocrinol (Lausanne) ; 15: 1327849, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006363

RESUMEN

Introduction: Previous observational studies have shown that polycystic ovary syndrome (PCOS) was associated with adverse pregnancy and perinatal outcomes. However, it remains controversial whether PCOS is an essential risk factor for these adverse pregnancy and perinatal outcomes. We aimed to use instrumental variables in a two-sample Mendelian randomization (MR) study to determine causality between PCOS and adverse pregnancy and perinatal outcomes. Materials and methods: Summary statistics were extracted from a recent genome-wide association study (GWAS) meta-analysis conducted in PCOS, which included 10,074 cases and 103,164 controls of European ancestry. Data on Adverse pregnancy and perinatal outcomes were summarized from the FinnGen database of European ancestry, which included more than 180,000 samples. The inverse variance weighted (IVW) method of MR was applied for the main outcome. To assess heterogeneity and pleiotropy, we conducted sensitivity analyses, including leave-one-out analysis, weighted median, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MR-Egger regression. Results: Two-sample MR analysis with the IVW method suggested that PCOS exerted causal effects on the risk of hypertensive disorders of pregnancy [odds ratio (OR) 1.170, 95% confidence interval (CI) 1.051-1.302, p = 0.004], in particular gestational hypertension (OR 1.083, 95% CI 1.007-1.164, p = 0.031), but not other pregnancy and perinatal diseases (all p > 0.05). Sensitivity analyses demonstrated pleiotropy only in pre-eclampsia or eclampsia (p = 0.0004), but not in other pregnancy and perinatal diseases (all p > 0.05). The results remained consistent after excluding two outliers (all p > 0.05). Conclusions: We confirmed a causal relationship between PCOS and hypertensive disorders of pregnancy, in particular gestational hypertension, but no association with any other adverse pregnancy or perinatal outcome. Therefore, we suggest that women with PCOS who are pregnant should have their blood pressure closely monitored.


Asunto(s)
Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Síndrome del Ovario Poliquístico , Resultado del Embarazo , Humanos , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/complicaciones , Femenino , Embarazo , Resultado del Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/genética , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/epidemiología , Factores de Riesgo , Recién Nacido , Polimorfismo de Nucleótido Simple
17.
Artículo en Inglés | MEDLINE | ID: mdl-39010714

RESUMEN

PURPOSE: (1) To determine the prevalence, magnitude and distribution pattern of acetabular rim ossification in patients with femoroacetabular impingement syndrome (FAIS) and (2) to determine the association between acetabular rim ossification and rotational abnormalities of the hip. METHODS: Patients underwent hip arthroscopic surgery for FAIS at our institute between January 2021 and May 2022 were retrospectively reviewed. Patients were included if preoperative computed tomography (CT) images of the operated hip and ipsilateral distal femur were available for the measurement of femoral and acetabular anteversion. The presence and size of acetabular rim ossification were evaluated on coronal CT sections for the superior half of the acetabulum on each clockface location. The associations between acetabular rim ossification and radiographic parameters of hip rotational morphology were examined. RESULTS: A total of 214 hips were included. Acetabular rim ossification was found in 167 hips (78%) and the most common locations were 10 and 11 o'clock. Patients presenting with acetabular rim ossification had a mean size of 4.6 ± 1.6 mm. It was the largest at 9 o'clock position (4.9 ± 2.2 mm), with a decreasing trend in size from posterior to anterior. Logistics regression analysis found age was associated with the occurrence of posterior ossification (p = 0.002). Linear regression analysis found age (p = 0.049) and male sex (p < 0.001) were significantly correlated with the size of ossification. Patients with increased cranial combined anteversion had larger posterior ossification than patients with normal and decreased cranial combined anteversion (4.2 ± 2.9 vs. 3.1 ± 2.5 mm, p = 0.016; 4.2 ± 2.9 vs. 2.5 ± 2.4 mm, p = 0.005). CONCLUSION: Increased combined anteversion is associated with greater posterior acetabular rim ossification. The presence and size of acetabular rim ossification are positively associated with older age and male sex. LEVEL OF EVIDENCE: Level III.

18.
Plant Cell ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39038209

RESUMEN

The level of methylesterification alters the functional properties of pectin, which is believed to influence plant growth and development. However, the mechanisms that regulate demethylesterification remain largely unexplored. Pectin with a high degree of methylesterification is produced in the Golgi apparatus and then transferred to the primary cell wall where it is partially demethylesterified by pectin methylesterases (PMEs). Here, we show that in Arabidopsis (Arabidopsis thaliana) seed mucilage, pectin demethylesterification is negatively regulated by the transcription factor ZINC FINGER FAMILY PROTEIN5 (ZAT5). Plants carrying null mutations in ZAT5 had increased PME activity, decreased pectin methylesterification, and produced seeds with a thinner mucilage layer. We provide evidence that ZAT5 binds to a TGATCA-motif and thereby negatively regulates methylesterification by reducing the expression of PME5, HIGHLY METHYL ESTERIFIED SEEDS (HMS)/PME6, PME12, and PME16. We also demonstrate that ZAT5 physically interacts with BEL1-LIKE HOMEODOMAIN2 (BLH2) and BLH4 transcription factors. BLH2 and BLH4 are known to modulate pectin demethylesterification by directly regulating PME58 expression. The ZAT5-BLH2/4 interaction provides a mechanism to control the degree of pectin methylesterification in seed coat mucilage by modifying each transcription factor's ability to regulate the expression of target genes encoding PMEs. Taken together, these findings reveal a transcriptional regulatory module comprising ZAT5, BLH2 and BLH4, that functions in modulating the de-methylesterification of homogalacturonan in seed coat mucilage.

19.
Plant Physiol Biochem ; 214: 108922, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39038384

RESUMEN

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) protein, named for its LATERAL ORGAN BOUNDARIES (LOB) domain, is a member of a class of specific transcription factors commonly found in plants and is absent from all other groups of organisms. LBD TFs have been systematically identified in about 35 plant species and are involved in regulating various aspects of plant growth and development. However, research on the signaling network and regulatory functions of LBD TFs is insufficient, and only a few members have been studied. Moreover, a comprehensive review of these existing studies is lacking. In this review, the structure, regulatory mechanism and function of LBD TFs in recent years were reviewed in order to better understand the role of LBD TFs in plant growth and development, and to provide a new perspective for the follow-up study of LBD TFs.

20.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3657-3667, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39041138

RESUMEN

This study aims to predict the possible targets and related signaling pathways of Modified Huoluo Xiaoling Pills against colorectal cancer(CRC) by both network pharmacology and molecular docking and verify the mechanism of action by experiments. TCMSP was used to obtain the active ingredients and targets of Modified Huoluo Xiaoling Pills, and GeneCards, DrugBank, OMIM, and TTD were employed to acquire CRC-related targets. Cytoscape software was utilized to construct the drug-active ingredient-target network, and the STRING database was applied to establish the protein-protein interaction(PPI) network. DAVID platform was adopted to investigate the targets in terms of GO function and KEGG pathway enrichment analysis. Molecular docking was performed in AutoDock Vina. HCT 116 cells were intervened by different concentrations of Modified Huoluo Xiaoling Pills-containing serum, and CCK-8 was used to detect the proliferation inhibition of HCT 116 cells in each group. Transwell was employed to show the invasive abi-lity of HCT 116 cells, and Western blot was taken to reveal the expression levels of ß-catenin, cyclinD1, c-Myc, as well as epithelial-mesenchymal transition(EMT) marker proteins E-cadherin, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST in HCT 116 cells. The network pharmacological analysis yielded 242 active ingredients of Modified Huoluo Xiaoling Pills, 1 844 CRC targets, and 127 overlapping targets of CRC and Modified Huoluo Xiaoling Pills, and the signaling pathways related to CRC involved PI3K-Akt, TNF, HIF-1, IL-17, Wnt, etc. Molecular docking showed that the key active ingredients had a stable binding conformation with the core proteins. CCK-8 indicated that Modified Huoluo Xiaoling Pills significantly inhibited the proliferation of HCT 116 cells. Transwell assay showed that with increasing concentration of Modified Huoluo Xiaoling Pills containing serum, the invasive ability of HCT 116 cells was more obviously inhibited. The expression of ß-catenin, cyclinD1, c-Myc, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST proteins were suppressed, and the expression of E-cadherin was improved by the intervention of drug-containing serum. Thus, it can be seen that Modified Huoluo Xiaoling Pills restrains the proliferation, invasion, and metastasis of CRC cells through multiple components, multiple targets, and multiple pathways, and the mechanism of action may be related to the inhibition of the activation of the Wnt/ß-catenin signaling pathway, thereby affecting the occurrence of EMT.


Asunto(s)
Proliferación Celular , Neoplasias Colorrectales , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Proliferación Celular/efectos de los fármacos , Células HCT116 , Transición Epitelial-Mesenquimal/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA