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1.
Cells ; 13(13)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38995009

RESUMEN

We developed an automated microregistration method that enables repeated in vivo skin microscopy imaging of the same tissue microlocation and specific cells over a long period of days and weeks with unprecedented precision. Applying this method in conjunction with an in vivo multimodality multiphoton microscope, the behavior of human skin cells such as cell proliferation, melanin upward migration, blood flow dynamics, and epidermal thickness adaptation can be recorded over time, facilitating quantitative cellular dynamics analysis. We demonstrated the usefulness of this method in a skin biology study by successfully monitoring skin cellular responses for a period of two weeks following an acute exposure to ultraviolet light.


Asunto(s)
Piel , Humanos , Piel/citología , Piel/diagnóstico por imagen , Rayos Ultravioleta , Rastreo Celular/métodos , Proliferación Celular , Movimiento Celular , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Microscopía/métodos
2.
bioRxiv ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38948784

RESUMEN

Mitochondrial creatine kinases are key players in maintaining energy homeostasis in cells by working in conjunction with cytosolic creatine kinases for energy transport from mitochondria to cytoplasm. High levels of MtCK observed in Her2+ breast cancer and inhibition of breast cancer cell growth by substrate analog, cyclocreatine, indicate dependence of cancer cells on the 'energy shuttle' for cell growth and survival. Hence, understanding the key mechanistic features of creatine kinases and their inhibition plays an important role in the development of cancer therapeutics. Herein, we present the mutational and structural investigation on understudied ubiquitous mitochondrial creatine kinase (uMtCK). Our cryo-EM structures and biochemical data on uMtCK showed closure of the loop comprising residue His61 is specific to and relies on creatine binding and the reaction mechanism of phosphoryl transfer depends on electrostatics in the active site. In addition, the previously identified covalent inhibitor CKi showed inhibition in breast cancer BT474 cells, however our biochemical and structural data indicated that CKi is not a potent inhibitor for breast cancer due to strong dependency on the covalent link formation and inability to induce conformational changes upon binding.

3.
Front Oncol ; 14: 1320220, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962264

RESUMEN

Background: Our previous studies have demonstrated that Raman spectroscopy could be used for skin cancer detection with good sensitivity and specificity. The objective of this study is to determine if skin cancer detection can be further improved by combining deep neural networks and Raman spectroscopy. Patients and methods: Raman spectra of 731 skin lesions were included in this study, containing 340 cancerous and precancerous lesions (melanoma, basal cell carcinoma, squamous cell carcinoma and actinic keratosis) and 391 benign lesions (melanocytic nevus and seborrheic keratosis). One-dimensional convolutional neural networks (1D-CNN) were developed for Raman spectral classification. The stratified samples were divided randomly into training (70%), validation (10%) and test set (20%), and were repeated 56 times using parallel computing. Different data augmentation strategies were implemented for the training dataset, including added random noise, spectral shift, spectral combination and artificially synthesized Raman spectra using one-dimensional generative adversarial networks (1D-GAN). The area under the receiver operating characteristic curve (ROC AUC) was used as a measure of the diagnostic performance. Conventional machine learning approaches, including partial least squares for discriminant analysis (PLS-DA), principal component and linear discriminant analysis (PC-LDA), support vector machine (SVM), and logistic regression (LR) were evaluated for comparison with the same data splitting scheme as the 1D-CNN. Results: The ROC AUC of the test dataset based on the original training spectra were 0.886±0.022 (1D-CNN), 0.870±0.028 (PLS-DA), 0.875±0.033 (PC-LDA), 0.864±0.027 (SVM), and 0.525±0.045 (LR), which were improved to 0.909±0.021 (1D-CNN), 0.899±0.022 (PLS-DA), 0.895±0.022 (PC-LDA), 0.901±0.020 (SVM), and 0.897±0.021 (LR) respectively after augmentation of the training dataset (p<0.0001, Wilcoxon test). Paired analyses of 1D-CNN with conventional machine learning approaches showed that 1D-CNN had a 1-3% improvement (p<0.001, Wilcoxon test). Conclusions: Data augmentation not only improved the performance of both deep neural networks and conventional machine learning techniques by 2-4%, but also improved the performance of the models on spectra with higher noise or spectral shifting. Convolutional neural networks slightly outperformed conventional machine learning approaches for skin cancer detection by Raman spectroscopy.

4.
Adv Mater ; : e2406347, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926947

RESUMEN

Electrical generation and transduction of polarized electron spins in semiconductors (SCs) are of central interest in spintronics and quantum information science. While spin generation in SCs is frequently realized via electrical injection from a ferromagnet (FM), there are significant advantages in nonmagnetic pathways of creating spin polarization. One such pathway exploits the interplay of electron spin with chirality in electronic structures or real space. Here, utilizing chirality-induced spin selectivity (CISS), the efficient creation of spin accumulation in n-doped GaAs via electric current injection from a normal metal (Au) electrode through a self-assembled monolayer (SAM) of chiral molecules (α-helix l-polyalanine, AHPA-L), is demonstrated. The resulting spin polarization is detected as a Hanle effect in the n-GaAs, which is found to obey a distinct universal scaling with temperature and bias current consistent with chirality-induced spin accumulation. The experiment constitutes a definitive observation of CISS in a fully nonmagnetic device structure and demonstration of its ability to generate spin accumulation in a conventional SC. The results thus place key constraints on the physical mechanism of CISS and present a new scheme for magnet-free SC spintronics.

5.
Front Plant Sci ; 15: 1355832, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721340

RESUMEN

Lycium barbarum L., commonly known as wolfberry, is not only a traditional Chinese medicine but also a highly nutritious food. Its main nutrients include L. barbarum polysaccharide, flavonoid polyphenols, carotenoids, alkaloids, and other compounds, demonstrating its wide application value. This study investigated the effects of nitrogen application on the accumulation of the main nutrients and metabolites in wolfberry fruits under three different nitrogen application rates, namely, N1 (20% nitrogen (N) reduction, 540 kg·ha-2), N2 (medium N, 675 kg·ha-2), and N3 (20% nitrogen increase, 810 kg·ha-2,which is a local conventional nitrogen application amount.). Additionally, due to continuous branching, blossoming, and fruiting of wolfberry plants during the annual growth period, this research also explored the variation in nutritional composition among different harvesting batches. The contents of total sugar and polysaccharide in wolfberry fruit were determined by Fehling reagent method and phenol-sulfuric acid method, respectively;The content of betaine in fruit was determined by high-performance liquid chromatography,and the flavonoids and carotene in the wolfberry fruits were determined by spectrophotometry. Analysis of data over three consecutive years revealed that as nitrogen application increased, the total sugar content in wolfberry fruits initially decreased and then increased. The levels of L. barbarum polysaccharides, total flavonoids, and total carotenoids initially increased and then decreased, while the betaine content consistently increased. Different picking batches significantly impacted the nutrient content of wolfberry fruits. Generally, the first batch of summer wolfberry fruits had greater amounts of total sugar and flavonoids, whereas other nutrients peaked in the third batch. By employing a broadly targeted metabolomics approach, 926 different metabolites were identified. The top 20 differentially abundant metabolites were selected for heatmap generation, revealing that the contents of L-citrulline, 2-methylglutaric acid, and adipic acid increased proportionally to the nitrogen gradient. Conversely, the dibutyl phthalate and 2, 4-dihydroxyquinoline contents significantly decreased under high-nitrogen conditions. The remaining 15 differentially abundant metabolites, kaempferol-3-O-sophorosid-7-O-rhamnoside, trigonelline, and isorhamnosid-3-O-sophoroside, initially increased and then decreased with increasing nitrogen levels. Isofraxidin, a common differentially abundant metabolite across all treatments, is a coumarin that may serve as a potential biomarker for wolfberry fruit response to nitrogen. Differentially abundant metabolites were analyzed for GO pathway involvement, revealing significant enrichment in metabolic pathways and biosynthesis of secondary metabolites under different nitrogen treatments. In conclusion, a nitrogen application of 675 kg·ha-2, 20% less than the local farmers' actual application, was most beneficial for the quality of four-year-old Ningqi 7 wolfberry fruits. Consumers who purchase wolfberry-dried fruit for health benefits should not consider only the first batch of summer wolfberry fruits. These results offer a broader perspective for enhancing the quality and efficiency of the wolfberry industry.

6.
Front Plant Sci ; 15: 1392175, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736439

RESUMEN

Wolfberry (Lycium, of the family Solanaceae) has special nutritional benefits due to its valuable metabolites. Here, 16 wolfberry-specific metabolites were identified by comparing the metabolome of wolfberry with those of six species, including maize, rice, wheat, soybean, tomato and grape. The copy numbers of the riboflavin and phenyllactate degradation genes riboflavin kinase (RFK) and phenyllactate UDP-glycosyltransferase (UGT1) were lower in wolfberry than in other species, while the copy number of the phenyllactate synthesis gene hydroxyphenyl-pyruvate reductase (HPPR) was higher in wolfberry, suggesting that the copy number variation of these genes among species may be the main reason for the specific accumulation of riboflavin and phenyllactate in wolfberry. Moreover, the metabolome-based neighbor-joining tree revealed distinct clustering of monocots and dicots, suggesting that metabolites could reflect the evolutionary relationship among those species. Taken together, we identified 16 specific metabolites in wolfberry and provided new insight into the accumulation mechanism of species-specific metabolites at the genomic level.

7.
ACS Appl Mater Interfaces ; 16(21): 27944-27951, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38764370

RESUMEN

Manipulating magnetization via power-efficient spin-orbit torque (SOT) has garnered significant attention in the field of spin-based memory and logic devices. However, the damping-like SOT efficiency (ξDL) in heavy metal (HM)/ferromagnetic metal (FM) bilayers is relatively small due to the strong spin dephasing accompanied by additional spin polarization decay. Furthermore, the perpendicular magnetic anisotropy (PMA) originating from the HM/FM interface is constrained by the thickness of FM, which is unfavorable for thermal stability in practical applications. Consequently, it is valuable to develop systems that not only exhibit large ξDL but also balance thermal stability. In this work, we designed antiferromagnetic-coupled [Co/Gd]N multilayers, where staggered Co and Gd magnetic moments effectively suppress the spin dephasing and additional spin polarization decay. The ordered Co-Gd arrangements along the out-of-plane direction provide bulk PMA, endowing Pt/[Co/Gd]N high thermal stability. The SOT of Pt/[Co/Gd]N was systematically studied with N, demonstrating a significantly large ξDL of up to 0.66. The ξDL of Pt/[Co/Gd]N is greater than those of Pt/Co and Pt/ferrimagnetic alloys. This significant enhancement relies on the effective suppression of spin dephasing in [Co/Gd]N. Our work highlights that the antiferromagnetic-coupled [Co/Gd]N multilayer is a promising candidate for low-consumption and high-density spintronic devices.

10.
Food Res Int ; 183: 114202, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38760133

RESUMEN

Pixian broad bean paste is a renowned fermented seasoning. The fermentation of broad bean is the most important process of Pixian broad bean paste. To enhance the flavor of tank-fermented broad bean paste, salt-tolerant Bacillus amyloliquefaciens strain was inoculated, resulting in an increase in total amount of volatile compounds, potentially leading to different flavor characteristics. To investigate the fermentation mechanism, monoculture simulated fermentation systems were designed. Metabolomics and transcriptomics were used to explore Bacillus amyloliquefaciens' transcriptional response to salt stress and potential aroma production mechanisms. The results highlighted different metabolite profiles under salt stress, and the crucial roles of energy metabolism, amino acid metabolism, reaction system, transportation system in Bacillus amyloliquefaciens' hypersaline stress response. This study provides a scientific basis for the industrial application of Bacillus amyloliquefaciens and new insights into addressing the challenges of poor flavor quality in tank fermentation products.


Asunto(s)
Bacillus amyloliquefaciens , Fermentación , Metabolómica , Bacillus amyloliquefaciens/metabolismo , Bacillus amyloliquefaciens/genética , Transcriptoma , Microbiología de Alimentos , Alimentos Fermentados/microbiología , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo , Perfilación de la Expresión Génica , Gusto , Fabaceae/microbiología
11.
J Am Heart Assoc ; 13(9): e033474, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38700020

RESUMEN

BACKGROUND: Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear. METHODS AND RESULTS: This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty-five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal-progressively-adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021-1.238], relative risk according to per interquartile increment was 1.039 [1.008-1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper-cadmium-lead mixture on subclinical carotid plaque presence. CONCLUSIONS: Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.


Asunto(s)
Enfermedades de las Arterias Carótidas , Cobre , Humanos , Femenino , Masculino , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Cobre/sangre , Persona de Mediana Edad , Factores de Riesgo , Anciano , Placa Aterosclerótica/sangre , Cadmio/sangre , Medición de Riesgo , China/epidemiología , Biomarcadores/sangre , Enfermedades Asintomáticas , Plomo/sangre
12.
J Agric Food Chem ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557018

RESUMEN

In this study, in silico analysis and peptidomics were performed to examine the generation mechanism of the umami taste of fermented broad bean paste (FBBP). Based on the information from peptidomics, a total of 470 free peptides were identified from FBBP, most of which were increased after fermentation. Additionally, the increase of the content of umami peptides, organic acids, and amino acids during fermentation contributed to the perception of umami taste in FBBP. Molecule docking results inferred that these umami molecules were easy to connect with Ser, Glu, His, and Gln in the T1R3 subunit through hydrogen bonds and electrostatic interaction force. The binding sites His145, Gln389, and Glu301 particularly contributed to the formation of the ligand-receptor complexes. The aromatic interaction, hydrogen bond, hydrophilicity, and solvent-accessible surface (SAS) played key roles in the receptor-peptide interaction. Sensory evaluation and electronic tongue results showed that EDEDE, DLSESV, SNGDDE, DETL, CDLSD, and TDEE screened from FBBP had umami characteristics and umami-enhancing effects (umami threshold values ranging from 0.131 to 0.394 mmol/L). This work provides new insight into the rapid and efficient screening of novel umami peptides and a deeper understanding of the taste mechanisms of umami molecules from FBBP.

13.
aBIOTECH ; 5(1): 17-28, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38576436

RESUMEN

Small RNA (sRNA)-mediated RNA silencing (also known as RNA interference, or RNAi) is a conserved mechanism in eukaryotes that includes RNA degradation, DNA methylation, heterochromatin formation and protein translation repression. In plants, sRNAs can move either cell-to-cell or systemically, thereby acting as mobile silencing signals to trigger noncell autonomous silencing. However, whether and what proteins are also involved in noncell autonomous silencing have not been elucidated. In this study, we utilized a previously reported inducible RNAi plant, PDSi, which can induce systemic silencing of the endogenous PDS gene, and we demonstrated that DCL3 is involved in systemic PDS silencing through its RNA binding activity. We confirmed that the C-terminus of DCL3, including the predicted RNA-binding domain, is capable of binding short RNAs. Mutations affecting RNA binding, but not processing activity, reduced systemic PDS silencing, indicating that DCL3 binding to RNAs is required for the induction of systemic silencing. Cucumber mosaic virus infection assays showed that the RNA-binding activity of DCL3 is required for antiviral RNAi in systemically noninoculated leaves. Our findings demonstrate that DCL3 acts as a signaling agent involved in noncell autonomous silencing and an antiviral effect in addition to its previously known function in the generation of 24-nucleotide sRNAs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00124-6.

14.
aBIOTECH ; 5(1): 114, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38576432

RESUMEN

[This corrects the article DOI: 10.1007/s42994-023-00124-6.].

15.
Food Chem ; 450: 139297, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38631199

RESUMEN

This study aimed to investigate the antioxidative and cytoprotective activity of antioxidant peptides from fermented broad bean paste (FBBP) and explore their potential molecular mechanisms using a combined in silico and in vitro approach. Seven novel antioxidant peptides (VSRRFIYYL, SPAIPLP, PVPPPGG, KKDGYWWAKFK, LAWY, LGFMQF, and LPGCP) identified by integrated approaches of peptidomics and in silico bioinformatic analysis were synthesized, exhibiting strong antioxidant potential against in vitro radicals. Molecular docking results suggested that these peptides could form stable hydrogen bonds and solvent-accessible surface with key amino acid residues of Keap1, thus potentially regulating the Keap1-Nrf2 pathway by occupying the Nrf2-binding site on Keap1. Additionally, they exhibited strong cellular antioxidant activity and could protect HepG2 cells from AAPH-induced oxidative injury by reducing reactive oxygen species and MDA accumulation. This study firstly unraveled the molecular mechanisms of antioxidant peptides from FBBP, and provided a new theoretical basis for the high-value utilization of FBBP.


Asunto(s)
Antioxidantes , Fermentación , Simulación del Acoplamiento Molecular , Péptidos , Antioxidantes/química , Antioxidantes/farmacología , Humanos , Péptidos/química , Péptidos/farmacología , Péptidos/metabolismo , Células Hep G2 , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/química , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/química , Proteína 1 Asociada A ECH Tipo Kelch/genética , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Simulación por Computador
16.
Front Immunol ; 15: 1319698, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646543

RESUMEN

This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02 g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.


Asunto(s)
Alimentación Animal , Antioxidantes , Suplementos Dietéticos , Metionina , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Metionina/administración & dosificación , Serina-Treonina Quinasas TOR/metabolismo , Antioxidantes/metabolismo , Alimentación Animal/análisis , Carpa Dorada/crecimiento & desarrollo , Carpa Dorada/genética , Carpa Dorada/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos
17.
BMC Psychiatry ; 24(1): 297, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641813

RESUMEN

BACKGROUND: This study aimed to investigate the interplay between anxiety and depressive symptoms in Chinese college freshmen using the causal system perspective (CSP), which differs from the traditional common cause perspective (CCP) by providing an alternative explanation by attributing comorbidity to direct interactions among symptoms. METHODS: A convenience sample of 2,082 Chinese college freshmen (39.51% male, Mage = 18.61) from a normal university completed the Generalized Anxiety Disorder 7-Item Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9). Network analysis was conducted and evaluated as to centrality, stability, node predictability, and bridging features. Moreover, the moderated network model (MNM) was utilized to detect the moderation effects of gender in the comorbidity network. RESULTS: The network of anxiety and depressive symptoms exhibited stability, characterized by the core symptoms of "restlessness", "lack of energy", and "excessive worry about control", as well as the bridging symptoms of "fearfulness", "sad mood", and "irritability". Notably, the nodes representing "uncontrollable worry" and "difficulty in relaxation" demonstrated the highest predictive power. Gender did not exert any moderating effects on the anxiety and depressive symptom network. CONCLUSION: These results reinforce that certain anxiety or depressive symptoms are more central than others, and thus play a more vital role in the comorbid network. These findings highlight underlying potential targeting symptoms to consider in future interventions.


Asunto(s)
Ansiedad , Depresión , Masculino , Humanos , Adolescente , Femenino , Depresión/diagnóstico , Depresión/epidemiología , Universidades , Ansiedad/epidemiología , Ansiedad/diagnóstico , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Comorbilidad
18.
Yi Chuan ; 46(4): 266-278, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38632090

RESUMEN

RNA silencing (or RNA interference, RNAi) is a conserved mechanism for regulating gene expression in eukaryotes, which plays vital roles in plant development and response to biotic and abiotic stresses. The discovery of trans-kingdom RNAi and interspecies RNAi provides a theoretical basis for exploiting RNAi-based crop protection strategies. Here, we summarize the canonical RNAi mechanisms in plants and review representative studies associated with plant-pathogen interactions. Meanwhile, we also elaborate upon the principles of host-induced gene silencing, spray-induced gene silencing and microbe-induced gene silencing, and discuss their applications in crop protection, thereby providing help to establish novel RNAi-based crop protection strategies.


Asunto(s)
Protección de Cultivos , Plantas , Interferencia de ARN , Plantas/genética , Eucariontes/genética , ARN Interferente Pequeño/genética
19.
Phytomedicine ; 129: 155612, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38669968

RESUMEN

BACKGROUND: Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a mere 10-30 %. The disruption of fibroblast growth factor receptor (FGFRs) signaling pathways is significantly implicated in the onset and advancement of CRC, presenting a promising target for therapeutic intervention in CRC management. Further investigation is essential to comprehensively elucidate FGFR1's function in CRC and to create potent therapies that specifically target FGFR1. PURPOSE: This study aims to demonstrate the oncogenic role of FGFR1 in colorectal cancer and to explore the potential of ß,ß-dimethylacrylalkannin (ß,ß-DMAA) as a therapeutic option to inhibit FGFR1. METHODS: In this research, we employed a comprehensive suite of techniques including tissue array, kinase profiling, computational docking, knockdown assay to predict and explore the inhibitor of FGFR1. Furthermore, we utilized kinase assay, pull-down, cell proliferation tests, and Patient derived xenograft (PDX) mouse models to further investigate a novel FGFR1 inhibitor and its impact on the growth of CRC. RESULTS: In our research, we discovered that FGFR1 protein is markedly upregulated in colorectal cancer tissues, suggesting a significant role in regulating cellular proliferation, particularly in patients with colorectal cancer. Furthermore, we conducted a computational docking, kinase profiling analysis, simulation and identified that ß,ß-DMAA could directly bind with FGFR1 within ATP binding pocket domain. Cell-based assays confirmed that ß,ß-DMAA effectively inhibited the proliferation of colon cancer cells and also triggered cell cycle arrest, apoptosis, and altered FGFR1-mediated signaling pathways. Moreover, ß,ß-DMAA effectively attenuated the development of PDX tumors in mice that were FGFR1-positive, with no notable toxicity observed. In summary, our study highlights the pivotal role of FGFR1 in colorectal cancer, suggesting that inhibiting FGFR1 activity could be a promising strategy for therapeutic intervention. We present strong evidence that targeting FGFR1 with ß,ß-DMAA is a viable approach for the management of colorectal cancer. Given its low toxicity and high efficacy, ß,ß-DMAA, as an FGFR1 inhibitor, warrants further investigation in clinical settings for the treatment of FGFR1-positive tumors.


Asunto(s)
Proliferación Celular , Neoplasias Colorrectales , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Animales , Femenino , Humanos , Ratones , Acrilamidas/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
20.
ACS Appl Mater Interfaces ; 16(13): 17041-17050, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38517684

RESUMEN

The ultrafast manipulation of spin in ferromagnet-semiconductor (FM/SC) heterojunctions is a key issue for advancing spintronics, where magnetic damping and interfacial spin transport often define device efficiency. Leveraging selective optical excitation in semiconductors offers a unique approach to spin manipulation in FM/SC heterojunctions. Herein, we investigated the magnetic dynamics of a Co2FeAl/n-GaAs heterojunction using the time-resolved magneto-optical Kerr technique and observed the considerably enhanced magnetic damping of Co2FeAl when GaAs is photoexcited near its band edge. This enhancement is attributed to an enhanced spin-pumping effect facilitated by spin-dependent carrier tunneling and capture within the Co2FeAl layer. Moreover, circularly polarized light excites spin-polarized band-edge photocarriers, further impacting the magnetic damping of Co2FeAl through an additional optical spin-transfer torque on the magnetic moment of Co2FeAl. Our results provide a valuable reference for manipulating spin-pumping and interfacial spin transport in FM/SC heterojunctions, showcasing the advantage of optical control of semiconductor photocarriers for the ultrafast manipulation of magnetic dynamics and interfacial spin transfer.

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