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1.
Materials (Basel) ; 17(19)2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39410320

RESUMEN

In this study, multi-element nitride coatings composed of (Ti, Cr, Cu, Al, Si)N were synthesized on H13 tool steel using cathodic arc deposition (CAD) technology. The N2/Ar flow ratio varied from 0 to 2 as the experimental parameter, and two targets, Ti-Cr-Cu and Al-Si alloys, were utilized simultaneously. The impact of the gas flow ratio on the coatings' abrasion properties was investigated, focusing on aspects, such as chemical composition, adhesion, hardness, and wear behavior. The experimental findings indicate that the coated specimens with a nitrogen reaction exhibit superior hardness and abrasion resistance compared to those without nitrogen use. While the surface roughness of the specimens tends to increase slightly with a higher N2/Ar ratio, the coating demonstrates improved hardness, adhesion, and abrasion resistance performance. In summary, the wear-resistant characteristics of H13 tool steel can be significantly enhanced when applying a CAD-(Ti, Cr, Cu, Al, Si)N film with a flow ratio of N2/Ar = 2.

2.
Ying Yong Sheng Tai Xue Bao ; 35(9): 2473-2482, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39435810

RESUMEN

Forest landscape model can quantitatively simulate the spatiotemporal variations in forest structure and function at the landscape scale based on traditional field survey data and mathematical models, providing a reference for the formulation of scientific forest management strategies. FireBGCv2 is one of the representative models currently used in the research area of forest landscape changes. It can simulate ecological processes at various scales, including trees scale (tree growth, establishment, and mortality), stand scale (carbon and nitrogen pools, fuel treatment, decomposition), site scale (resource competition and species phenology), and landscape scale (seed dispersal and wildfire disturbances), and the effects of those processes on forest landscape structure and function. The advantage of this model lies in its ability to simulate multiple ecological processes while considering the diversity and complexity of ecosystems. However, it also has drawbacks, such as high computational demands and complexity of use. We summarized the basic principles and structure of FireBGCv2 and introduced its application progress in forest landscape research and management. Currently, the application of the FireBGCv2 model, both domestically and internationally, mainly focused on exploring the interactions between fire, climate, and vegetation, quantifying the spatial and temporal dynamics of fires, and describing potential fire dynamics under future climate scenarios and land management strategies. With the in-depth development of forest landscape model theories and applications, the future prospects of FireBGCv2 include improving and updating the model's algorithms, adding new functional modules to explore fire management issues, and meeting the needs of different users.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Bosques , Modelos Teóricos , Árboles , Árboles/crecimiento & desarrollo , Conservación de los Recursos Naturales/métodos , Incendios , Simulación por Computador
3.
ACS Biomater Sci Eng ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39403768

RESUMEN

Compared with traditional high-density cell spheroids, which are more prone to core necrosis, nanowires effectively improve the biological activity of core cells in spheroids, emanating more innovations for optimizing the internal cell survival environment and providing differentiation signals. In this study, hydroxyapatite nanowires (HAW), which provide numerous material exchange channels for internal cells by interpenetrating into cell spheroids, were added to osteoblast precursor (MC3T3-E1) cell spheroids. HAW, synthesized using the hydrothermal method, was used as a regulatory material to prepare uniformly sized 3D composite spheroids with good biological activity. Subsequently, material characterization and biocompatibility tests were performed on HAW, and the biological activity and osteogenic differentiation ability of the cell spheroids were tested. Notably, in 2D coculture, HAW displayed a certain attraction to MC3T3-E1 cells and promoted cell aggregation toward it. The content of HAW determined whether composite cell spheroids can form aggregated spherical structures, and incorporation of HAW alleviated core necrosis and enhanced the osteogenic phenotype. In summary, these findings indicate that the prepared HAW-bone cell composite spheroids can potentially be used as building blocks for the construction of large high-density biomimetic tissues and organoids using 3D bioprinting technology.

4.
J Tradit Complement Med ; 14(5): 568-580, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39262662

RESUMEN

Background and aim: A surplus of glucocorticoids (GC) is a main cause of non-traumatic osteonecrosis of the femoral head (ONFH), and Jintiange (JTG), as one of the traditional Chinese medicines (TCM), also plays an instrumental role in the alleviation of bone loss simultaneously. Therefore, JTG was thought to be able to reverse GC-induced ONFH (GC-ONFH) to a certain extent. Experimental procedure: In vivo, the effect of JTG on trabeculae in the subchondral bone of the femoral head was investigated using micro-computed tomography (micro-CT), TdT-mediated dUTP nick end labeling (TUNEL) and histological staining; in vitro, proliferation, viability, apoptosis, and senescence of purified bone mesenchymal stem cells (BMSCs) were examined to demonstrate the direct impact of JTG on these cells. Meanwhile after using a series of interventions, the function of JTG on BMSC differentiation could be assessed by measuring of osteogenic and adipogenic markers at levels of protein and mRNA. Results: Our final results demonstrated that with the involvement of Wnt/ß-catenin pathway, JTG was able to significantly promote osteogenesis, restrain adipogenesis, delay senescence in BMSCs, reduce osteoclast number, weaken apoptosis, and enhance proliferation of osteocytes, all of which could mitigate the progression of subchondral osteonecrosis. Conclusion: According to the results of experiments in vitro and vivo, JTG was deemed to relieve the early GC-ONFH using the prevention of destruction of subchondral bone, which was contributed to regulating the differentiation of BMSCs and the number of osteoclasts.

5.
Light Sci Appl ; 13(1): 263, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39300063

RESUMEN

Artificial intelligence has prevailed in all trades and professions due to the assistance of big data resources, advanced algorithms, and high-performance electronic hardware. However, conventional computing hardware is inefficient at implementing complex tasks, in large part because the memory and processor in its computing architecture are separated, performing insufficiently in computing speed and energy consumption. In recent years, optical neural networks (ONNs) have made a range of research progress in optical computing due to advantages such as sub-nanosecond latency, low heat dissipation, and high parallelism. ONNs are in prospect to provide support regarding computing speed and energy consumption for the further development of artificial intelligence with a novel computing paradigm. Herein, we first introduce the design method and principle of ONNs based on various optical elements. Then, we successively review the non-integrated ONNs consisting of volume optical components and the integrated ONNs composed of on-chip components. Finally, we summarize and discuss the computational density, nonlinearity, scalability, and practical applications of ONNs, and comment on the challenges and perspectives of the ONNs in the future development trends.

6.
Brain Behav ; 14(10): e70058, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39344357

RESUMEN

BACKGROUND: The monocyte-lymphocyte ratio (MLR) is a hematological test parameter that reflects the status of both monocytes and lymphocytes as inflammatory cells. This study aims to investigate the relationship between MLR and carotid intraplaque neovascularization (IPN) in patients with asymptomatic carotid stenosis. METHODS: We performed the Angio Planewave Ultrasensitive (AngioPLUS) screening for patients with carotid plaques. The carotid plaque stability was evaluated by semiquantitative visual grading of carotid IPN. Binary logistic regression models were performed to determine the associations between different clinical and laboratory indicators and the presence of high IPN. RESULTS: A total of 160 patients were eventually enrolled with 99 in the low IPN group (Scores 0-1) and 61 in the high IPN group (Score 2). Univariate logistic regression showed that age, monocytes, lymphocytes, glycated hemoglobin (HbA1c), fibrinogen, d-dimmer, and MLR were significantly associated with the presence of high IPN (all p < 0.05). Multivariate logistic regression models showed that MLR was significantly associated with the presence of high IPN after adjusting for other covariates. An MLR value of 32.9 was the optimal cutoff value to differentiate high and low IPN. High MLR was also significantly correlated with the presence of high IPN (odds ratio [OR] = 4.08, 95% confidence interval [CI]: 1.69-9.88, p = 0.002) when included in the above multivariate logistic regression model. CONCLUSION: Elevated MLR is closely associated with the presence of high IPN and may serve as a surrogate biomarker for carotid IPN.


Asunto(s)
Estenosis Carotídea , Linfocitos , Monocitos , Neovascularización Patológica , Humanos , Masculino , Femenino , Anciano , Estenosis Carotídea/sangre , Estenosis Carotídea/diagnóstico por imagen , Persona de Mediana Edad , Neovascularización Patológica/sangre , Neovascularización Patológica/patología , Placa Aterosclerótica/sangre , Placa Aterosclerótica/patología , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología
7.
Heliyon ; 10(14): e34262, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39113951

RESUMEN

Recent advancements in natural language processing, computational linguistics, and Artificial Intelligence (AI) have propelled the use of Large Language Models (LLMs) in Automated Essay Scoring (AES), offering efficient and unbiased writing assessment. This study assesses the reliability of LLMs in AES tasks, focusing on scoring consistency and alignment with human raters. We explore the impact of prompt engineering, temperature settings, and multi-level rating dimensions on the scoring performance of LLMs. Results indicate that prompt engineering significantly affects the reliability of LLMs, with GPT-4 showing marked improvement over GPT-3.5 and Claude 2, achieving 112% and 114% increase in scoring accuracy under the criteria and sample-referenced justification prompt. Temperature settings also influence the output consistency of LLMs, with lower temperatures producing scores more in line with human evaluations, which is essential for maintaining fairness in large-scale assessment. Regarding multi-dimensional writing assessment, results indicate that GPT-4 performs well in dimensions regarding Ideas (QWK=0.551) and Organization (QWK=0.584) under well-crafted prompt engineering. These findings pave the way for a comprehensive exploration of LLMs' broader educational implications, offering insights into their capability to refine and potentially transform writing instruction, assessment, and the delivery of diagnostic and personalized feedback in the AI-powered educational age. While this study attached importance to the reliability and alignment of LLM-powered multi-dimensional AES, future research should broaden its scope to encompass diverse writing genres and a more extensive sample from varied backgrounds.

8.
Phys Rev E ; 110(1): L012802, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39160931

RESUMEN

A steel ball with a density higher than that of water can bounce on a water surface when heated to a temperature well above the Leidenfrost point. In this letter, an experiment is conducted where heated steel balls are released onto a water surface. The heated steel ball descends into the liquid, thus causing the liquid to evaporate and form a vapor cushion with an upward force that lifts the steel ball. Subsequently, the steel ball bounces off the water surface, like a solid ball bouncing off an elastic surface without sinking into the water. This phenomenon is known as the inverse Leidenfrost effect. In this letter, we evaluate the various motion behaviors of spheres at different Reynolds numbers and temperatures. Additionally, we analyze the bouncing behavior of solid spheres on a free liquid surface and examine the various force components.

9.
Front Cell Infect Microbiol ; 14: 1406429, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39211795

RESUMEN

Dairy mastitis is one of the most common diseases in dairy farming, and the formation of pathogenic bacteria biofilms may be an important reason why traditional antibiotic therapy fails to resolve some cases of dairy mastitis. We isolated and identified three strains of A. lwoffii were with strong biofilm forming ability from dairy cow mastitis samples from Chongqing dairy farms in China. In order to investigate the effect of novel anti-biofilm peptide CRAMP-34 on A.lwoffii biofilms, the anti-biofilm effect was evaluated by crystal violet staining, biofilms viable bacteria counting and confocal laser scanning microscopy (CLSM). In addition, transcriptome sequencing analysis, qRT-PCR and phenotypic verification were used to explore the mechanism of its action. The results showed that CRAMP-34 had a dose-dependent eradicating effect on A. lwoffii biofilms. Transcriptome sequencing analysis showed that 36 differentially expressed genes (11 up-regulated and 25 down-regulated) were detected after the intervention with the sub-inhibitory concentration of CRAMP-34. These differentially expressed genes may be related to enzyme synthesis, fimbriae, iron uptake system, capsular polysaccharide and other virulence factors through the functional analysis of differential genes. The results of subsequent bacterial motility and adhesion tests showed that the motility of A.lwoffii were enhanced after the intervention of CRAMP-34, but there was no significant change in adhesion. It was speculated that CRAMP-34 may promote the dispersion of biofilm bacteria by enhancing the motility of biofilm bacteria, thereby achieving the effect of eradicating biofilms. Therefore, these results, along with our other previous findings, suggest that CRAMP-34 holds promise as a new biofilm eradicator and deserves further research and development.


Asunto(s)
Acinetobacter , Antibacterianos , Biopelículas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Animales , Bovinos , Femenino , Acinetobacter/efectos de los fármacos , Acinetobacter/genética , Antibacterianos/farmacología , China , Mastitis Bovina/microbiología , Mastitis Bovina/tratamiento farmacológico , Adhesión Bacteriana/efectos de los fármacos , Perfilación de la Expresión Génica , Pruebas de Sensibilidad Microbiana , Infecciones por Acinetobacter/microbiología
10.
Int J Mol Sci ; 25(16)2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39201560

RESUMEN

Faba bean is an important pulse. It provides proteins for the human diet and is used in industrial foodstuffs, such as flours. Drought stress severely reduces the yield of faba bean, and this can be efficiently overcome through the identification and application of key genes in response to drought. In this study, PacBio and Illumina RNA sequencing techniques were used to identify the key pathways and candidate genes involved in drought stress response. During seed germination, a total of 17,927 full-length transcripts and 12,760 protein-coding genes were obtained. There were 1676 and 811 differentially expressed genes (DEGs) between the varieties E1 and C105 at 16 h and 64 h under drought stress, respectively. Six and nine KEGG pathways were significantly enriched at 16 h and 64 h under drought stress, which produced 40 and 184 nodes through protein-protein interaction (PPI) analysis, respectively. The DEGs of the PPI nodes were involved in the ABA (abscisic acid) and MAPK (mitogen-activated protein kinase) pathways, N-glycosylation, sulfur metabolism, and sugar metabolism. Furthermore, the ectopic overexpression of a key gene, AAT, encoding aspartate aminotransferase (AAT), in tobacco, enhanced drought tolerance. The activities of AAT and peroxidase (POD), the contents of cysteine and isoleucine, were increased, and the contents of malonaldehyde (MDA) and water loss decreased in the overexpressed plants. This study provides a novel insight into genetic response to drought stress and some candidate genes for drought tolerance genetic improvements in this plant.


Asunto(s)
Sequías , Regulación de la Expresión Génica de las Plantas , Germinación , Semillas , Estrés Fisiológico , Vicia faba , Vicia faba/genética , Vicia faba/crecimiento & desarrollo , Germinación/genética , Estrés Fisiológico/genética , Semillas/genética , Semillas/crecimiento & desarrollo , Análisis de Secuencia de ARN/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica/métodos , Mapas de Interacción de Proteínas/genética , Transcriptoma/genética
11.
Heliyon ; 10(15): e35507, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39166026

RESUMEN

Optical paths in telescopes frequently incorporate silver mirrors for high sensitivity. Unfortunately, silver mirrors without protective coatings are susceptible to sulfurization and oxidation, compromising their quality. Even with protective layers, insufficient adhesion between the coating and the silver film can lead to peeling, exposing the silver to external environments and affecting its quality. This study aimed to identify dielectric materials with superior adhesion to silver, rendering them ideal choices for silver coating applications. By electron gun evaporation, different dielectric layers were deposited on the top and bottom of the silver film under a substrate temperature below 150 °C. These coatings were composed of materials with desired refractive indices, including aluminum oxide (Al2O3), aluminum-doped silicon, magnesium fluoride (MgF2), and other dielectrics. Following the deposition, a tape adhesion test was conducted to evaluate the bond strength of the samples. X-ray photoelectron spectroscopy (XPS) analysis was carried out to investigate the interaction between silver and its neighboring layers. The results revealed that Al2O3 and MgF2 exhibited exceptional adhesion to silver. Moreover, these multilayer coatings can effectively enhance the reflectance of silver in the visible (VIS) wavelength ranges.

12.
Bioresour Technol ; 411: 131271, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39142418

RESUMEN

A multi-stage oxic biofilm system based on hydrophilic polyurethane foam was established and operated for advanced treatment of coking wastewater, in which distinct gradient variations of pollutants removal, biofilm properties and microbial community in the 5 stages were evaluated. The system rapidly achieved NH4+-N removal efficiency of 97.51 ±â€¯2.29 % within 8 days. The biofilm growing attached on the carriers exhibited high biomass (≥10.29 g/L), which ensured sufficient microbial population. Additionally, the rising extracellular polymeric substance and declining proteins/polysaccharides ratios across stages suggested a dense-to-loose transition in the biofilm's structure, in response to the varying pollutant concentrations. The dominance of Nitrosomonas cluster in the first 3 stages and Nitrospira lineage in the following 2 stages facilitated the complete depletion of high NH4+-N concentration without NO2--N accumulation. Overall, the distinct biofilm property and community at each stage, shaped by the multi-stage configuration, maximized the pollutants removal efficiency.


Asunto(s)
Biopelículas , Coque , Aguas Residuales , Aguas Residuales/química , Contaminantes Químicos del Agua , Reactores Biológicos , Proyectos Piloto , Purificación del Agua/métodos , Poliuretanos/química , Eliminación de Residuos Líquidos/métodos , Biodegradación Ambiental , Microbiota , Biomasa , Nitrógeno , Compuestos de Amonio
13.
Foods ; 13(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38998476

RESUMEN

To learn more about the nutritional composition and health benefits for human consumers of peas, we used a widely targeted metabolomics-based approach to reveal the metabolite components from three main varieties, and a total of 1095 metabolites were identified. A comparison of 487 differentially accumulated metabolites shared among three varieties of fresh and dried peas found most of the amino acids and derivatives were downregulated and most of the lipids and flavonoids were upregulated in dried peas. Furthermore, comparing the main nutrient profiles exclusively showed that there were few differences in free fatty acids, sugars, vitamins, and alkaloids between dried and fresh peas. Peas are especially enriched with B-group vitamins. Through detailed identification and classification, the flavonoid pathway of peas was revealed; a variety of glycosylated derivatives from kaempferol, quercetin, and luteolin were confirmed to be abundant in peas. It was also found that isoflavones are richer in peas than in many other plants, and putatively the isoflavone synthesis pathway originates from liquiritigenin and naringenin. Our study not only offers guidance for understanding the nutritional components of peas, but also provides the basis for healthy diet analysis of the edible value and health benefits of peas.

14.
Lupus Sci Med ; 11(2)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39053932

RESUMEN

OBJECTIVE: To investigate the role of curcumin in the treatment of lupus nephritis (LN) by inhibiting the migration of neutrophils and the underlying mechanism involved. METHODS: Two lupus mouse models, MRL/lpr mice and R848-treated mice, were treated with 50 mg/kg curcumin by intraperitoneal injection. H&E and Masson staining were used to estimate histopathological changes in the kidney. Immunofluorescence was used to assess the deposition of immune complexes. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription polymerase reaction (RT-PCR), and the protein expression was detected by western blotting. RESULTS: We revealed the remarkable potential of curcumin in improving inflammatory conditions in both MRL/lpr mice and R848-induced lupus mice. Curcumin effectively decelerates the progression of inflammation and diminishes the infiltration of neutrophils and their release of pivotal inflammatory factors, thereby reducing inflammation in renal tissues. Mechanistically, curcumin significantly inhibits the expression of p-PI3K, p-AKT and p-NF-κB, which are upregulated by interleukin-8 to induce neutrophil migration and renal inflammation, thereby reducing neutrophil migration and the release of inflammatory factors. CONCLUSION: Curcumin significantly inhibits the recruitment of neutrophils and the release of proinflammatory factors in the kidney by inhibiting the PI3K/AKT/NF-κB signalling pathway, providing new therapeutic targets and medication strategies for the treatment of LN.


Asunto(s)
Movimiento Celular , Curcumina , Nefritis Lúpica , FN-kappa B , Neutrófilos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Curcumina/farmacología , Curcumina/uso terapéutico , Animales , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Nefritis Lúpica/metabolismo , Nefritis Lúpica/inmunología , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Neutrófilos/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Movimiento Celular/efectos de los fármacos , Femenino , Modelos Animales de Enfermedad , Ratones Endogámicos MRL lpr , Riñón/efectos de los fármacos , Riñón/patología
15.
Sci Adv ; 10(30): eado8516, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058775

RESUMEN

Moving computation units closer to sensors is becoming a promising approach to addressing bottlenecks in computing speed, power consumption, and data storage. Pre-sensor computing with optical neural networks (ONNs) allows extensive processing. However, the lack of nonlinear activation and dependence on laser input limits the computational capacity, practicality, and scalability. A compact and passive multilayer ONN (MONN) is proposed, which has two convolution layers and an inserted nonlinear layer, performing pre-sensor computations with designed passive masks and a quantum dot film for incoherent light. MONN has an optical length as short as 5 millimeters, two orders of magnitude smaller than state-of-the-art lens-based ONNs. MONN outperforms linear single-layer ONN across various vision tasks, off-loading up to 95% of computationally expensive operations into optics from electronics. Motivated by MONN, a paradigm is emerging for mobile vision, fulfilling the demands for practicality, miniaturization, and low power consumption.

16.
Ultrasound Med Biol ; 50(10): 1585-1592, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39068137

RESUMEN

OBJECTIVE: The purpose of this study was to analyze the independent risk factors of malignant subpleural pulmonary lesions (SPLs) on B-mode ultrasound (US) images, to construct the combined predictive indicators, and to prospectively verify their predictive efficacy. METHODS: A total of 336 patients with SPLs were included in the prospective study, of whom the single-center included patients between September 2019 and December 2019 were the development cohort (DC) (n = 219); Patients who were concurrently enrolled in three centers between January and February 2020 were the validation cohort (VC) (n = 117). The clinical features and B-mode US parameters were collected. Based on the DC, a combined predictive indicators model was developed using binary logistic regression. Then the discrimination was verified externally in the VC. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians. RESULTS: The combined predictive indicators model was finally constructed by five parameters: age, borderline, angle between the lesion border and thoracic wall, posterior echo of the lesion and invasion of the pleura. The fitting degree of the model was good (χ2 = 9.198, p = 0.326). The area under ROC curve of the model was 0.872 (DC) and 0.808 (VC), yielding a higher net benefit than individual risk factors. CONCLUSION: The combined predictive indicators are useful in the assessment of malignant SPLs and are a useful adjunct diagnostic tool, especially in primary healthcare settings in developing countries.


Asunto(s)
Neoplasias Pulmonares , Valor Predictivo de las Pruebas , Ultrasonografía , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ultrasonografía/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Anciano , Adulto , Pulmón/diagnóstico por imagen , Diagnóstico Diferencial , Factores de Riesgo
17.
World J Exp Med ; 14(2): 88867, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38948422

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women. Currently, glucocorticoids and immunosuppressants are widely used to treat SLE patients. However, ovarian dysfunction occurs following the use of these drugs in women with SLE. Here, we summarize recent progress in terms of understanding ovarian injury, the effects of drug application and strategies to improve ovarian function in women with SLE. This review could be helpful to precisely cure SLE in women desiring to have offspring.

18.
Adv Sci (Weinh) ; 11(38): e2406333, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38981044

RESUMEN

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.


Asunto(s)
Apolipoproteína C-II , Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Lipólisis , Neoplasias Pulmonares , Animales , Femenino , Humanos , Ratones , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Modelos Animales de Enfermedad , Inmunoterapia/métodos , Lipólisis/efectos de los fármacos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/tratamiento farmacológico , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos
19.
Sci Rep ; 14(1): 14123, 2024 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898093

RESUMEN

Cytosolic Glycerol-3-phosphate dehydrogenase 1 (GPD1, EC 1.1.1.8) plays a pivotal role in regulating the Embden-Meyerhof glucose glycolysis pathway (E-M pathway), as well as in conditions such as Huntington's disease, cancer, and its potential role as a specific marker for Dormant Glioma Stem Cells. In this study, we conducted virtual screening using the ZINC database ( http://zinc.docking.org/ ) and the GPD1 structure to identify potential GPD1 modulators. The investigation involved screening active candidate ligands using ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters, combined with molecular docking, pose analysis, and interaction analysis based on Lipinski and Veber criteria. Subsequently, the top 10 ligands were subjected to 200 ns all-atom molecular dynamics (M.D.) simulations, and binding free energies were calculated. The findings revealed that specific residues, namely TRP14, PRO94, LYS120, ASN151, THR264, ASP260, and GLN298, played a crucial role in ensuring system stability. Furthermore, through a comprehensive analysis involving molecular docking, molecular M.D., and DeLA-Drug, we identified 10 promising small molecules. These molecules represent potential lead compounds for developing effective therapeutics targeting GPD1-associated diseases, thereby contributing to a deeper understanding of GPD1-associated mechanisms. This study's significance lies in identifying key residues associated with GPD1 and discovering valuable small molecules, providing a foundation for further research and development.


Asunto(s)
Glicerolfosfato Deshidrogenasa , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Humanos , Ligandos , Glicerolfosfato Deshidrogenasa/metabolismo , Glicerolfosfato Deshidrogenasa/química , Unión Proteica , Termodinámica , Sitios de Unión
20.
J Ethnopharmacol ; 333: 118438, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38848972

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear. AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia. MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses. RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice. CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.


Asunto(s)
Microbioma Gastrointestinal , Hiperlipidemias , Simulación del Acoplamiento Molecular , , Animales , Hiperlipidemias/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ratones , Té/química , Biología Computacional , Farmacología en Red , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones Endogámicos C57BL , Metabolismo de los Lípidos/efectos de los fármacos , Hipolipemiantes/farmacología , Hipolipemiantes/aislamiento & purificación , Hipolipemiantes/uso terapéutico , Modelos Animales de Enfermedad , Metabolómica , Multiómica
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