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Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.
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The impact of microplastics (MPs) as emerging pollutants on plant heavy metal toxicity has been extensively reported in vegetable-soil systems over recent years. However, little attention has been given to cultivar variations between degradable and non-degradable MPs. This study investigated the effects of degradable polylactic acid (PLA) and nondegradable polypropylene (PP) MPs on plant growth and biomarker (malonaldehyde (MDA) and antioxidant enzymes) performance in Cd-contaminated arable soil. The results show that both types of MPs significantly impacted plant biomass and biomarker contents across all three Cd levels. The degree of impact was significantly sensitive to both the type and dose of MPs, as they reduced the soil pH and cation exchange capacity (CEC) while increasing soil dissolved organic carbon (DOC), microbial biomass carbon, and nitrogen. PP exhibited greater root growth inhibition and phytotoxicity at higher doses of 1% and 5% compared to PLA. Specifically, the highest MDA contents were 1.44 and 2.20 mmol mg-1 protein for shoots and roots, respectively, in the 5% PLA treatment under a 10.1 mg kg-1 Cd level, which were 1.22 and 1.18 times higher than those in corresponding treatments of 5% PP. Overall, PLA had less significant effects on plant phytotoxicity, Cd availability, and soil properties compared to PP. Regression pathway analysis indicated that MPs increased shoot Cd uptake by altering both soil physical-chemical and microbial characteristics. Among the soil variables, pH, CEC, and Cd bioavailability were found to play vital roles. Yet, no single variable acts alone in the mechanism for plant Cd uptake. PLAs are suggested to replace conventional non-biodegradable plastics to control environmental MP pollution, particularly in agricultural systems with higher Cd contamination. However, the long-term effects of the by-products generated during the biodegradation process require further investigation.
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PURPOSE: A novel nomogram incorporating artificial intelligence (AI) and clinical features for enhanced ultrasound prediction of benign and malignant breast masses. MATERIALS AND METHODS: This study analyzed 340 breast masses identified through ultrasound in 308 patients. The masses were divided into training (n = 260) and validation (n = 80) groups. The AI-based analysis employed the Samsung Ultrasound AI system (S-detect). Univariate and multivariate analyses were conducted to construct nomograms using logistic regression. The AI-Nomogram was based solely on AI results, while the ClinAI- Nomogram incorporated additional clinical factors. Both nomograms underwent internal validation with 1000 bootstrap resamples and external validation using the independent validation group. Performance was evaluated by analyzing the area under the receiver operating characteristic (ROC) curve (AUC) and calibration curves. RESULTS: The ClinAI-Nomogram, which incorporates patient age, AI-based mass size, and AI-based diagnosis, outperformed an existing AI-Nomogram in differentiating benign from malignant breast masses. The ClinAI-Nomogram surpassed the AI-Nomogram in predicting malignancy with significantly higher AUC scores in both training (0.873, 95% CI: 0.830-0.917 vs. 0.792, 95% CI: 0.748-0.836; p = 0.016) and validation phases (0.847, 95% CI: 0.763-0.932 vs. 0.770, 95% CI: 0.709-0.833; p < 0.001). Calibration curves further revealed excellent agreement between the ClinAI-Nomogram's predicted probabilities and actual observed risks of malignancy. CONCLUSION: The ClinAI- Nomogram, combining AI alongside clinical data, significantly enhanced the differentiation of benign and malignant breast masses in clinical AI-facilitated ultrasound examinations.
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Inteligencia Artificial , Neoplasias de la Mama , Nomogramas , Ultrasonografía Mamaria , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Ultrasonografía Mamaria/métodos , Adulto , Anciano , Mama/diagnóstico por imagen , Diagnóstico Diferencial , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Nowadays, medical polyurethanes with favorable and durable antibacterial properties received more attention, because of avoiding repeated replacement of interventional materials and reducing patients' pain. In this thesis, non-soluble antibacterial polyurethane (NAPU) based on cation antibacterial mechanism was prepared by photo-grafting chitosan azide and heparin azide into polyurethane (PU). -NH3+of chitosan azide absorbed bacteria, inhibiting and breaking their mobility and structures. Heparin azide prevented cations from penetrating bacteria's membranes and inhibited their growth. The results showed that chitosan azide and heparin azide were successfully grafted into PU. The highest antibacterial rate was 92.07%, cytotoxicity grade ranging from 0-1 (RGR standard) and water contact angle exhibiting 60°, attributing to cation antibacterial effect and -OH existing. Tensile strength was up to 23.91 MPa and was suitable for using as medical materials. NAPU with long-lasting coating both possessed antibacterial properties and persistence, which can solve the problem of medical catheters' long-term using.
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Antibacterianos , Azidas , Cationes , Quitosano , Heparina , Poliuretanos , Poliuretanos/química , Quitosano/química , Antibacterianos/farmacología , Antibacterianos/química , Heparina/química , Azidas/química , Ensayo de Materiales , Resistencia a la Tracción , Escherichia coli/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Humanos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Ratones , SolubilidadRESUMEN
The cleavage of C-O bonds is one of the most promising strategies for lignin-to-chemicals conversion, which has attracted considerable attention in recent years. However, current catalytic system capable of selectively breaking C-O bonds in lignin often requires a precious metal catalyst and/or harsh conditions such as high-pressure H2 and elevated temperatures. Herein, we report a novel protocol of paired electrolysis to effectively cleave the Cß-O-4 bond of lignin model compounds and real lignin at room temperature and ambient pressure. For the first time, "cathodic hydrogenolysis of Cß-O-4 linkage" and "anodic C-H/N-H cross-coupling reaction" are paired in an undivided cell, thus the cleavage of C-O bonds and the synthesis of valuable triarylamine derivatives could be simultaneously achieved in an energy-effective manner. This protocol features mild reaction conditions, high atom economy, remarkable yield with excellent chemoselectivity, and feasibility for large-scale synthesis. Mechanistic studies indicate that indirect H* (chemical absorbed hydrogen) reduction instead of direct electron transfer might be the pathway for the cathodic hydrogenolysis of Cß-O-4 linkage.
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Despite medical advances, there remains an unmet need for better treatment of obesity. Itaconate, a product of the decarboxylation of the tricarboxylic acid cycle intermediate cis-aconitate, plays a regulatory role in both metabolism and immunity. Here, we show that itaconate, as an endogenous compound, counteracts high-fat-diet (HFD)-induced obesity through leptin-independent mechanisms in three mouse models. Specifically, itaconate reduces weight gain, reverses hyperlipidemia, and improves glucose tolerance in HFD-fed mice. Additionally, itaconate enhances energy expenditure and the thermogenic capacity of brown adipose tissue (BAT). Unbiased proteomic analysis reveals that itaconate upregulates key proteins involved in fatty acid oxidation and represses the expression of lipogenic genes. Itaconate may provoke a major metabolic reprogramming by inducing fatty acid oxidation and suppression of fatty acid synthesis in BAT. These findings highlight itaconate as a potential activator of BAT-mediated thermogenesis and a promising candidate for anti-obesity therapy.
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Adipocitos Marrones , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Obesidad , Succinatos , Termogénesis , Animales , Termogénesis/efectos de los fármacos , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Succinatos/farmacología , Dieta Alta en Grasa/efectos adversos , Ratones , Masculino , Adipocitos Marrones/metabolismo , Adipocitos Marrones/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Metabolismo Energético/efectos de los fármacosRESUMEN
BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) often have the condition of malnutrition, which can be presented as sarcopenia, micronutrient deficiencies, etc. Trace elements (magnesium, calcium, iron, copper, zinc, plumbum and manganese) belonging to micronutrients, are greatly vital for the assessment of nutritional status in humans. Trace element deficiencies are also the main manifestation of malnutrition. Calcium (Ca) has been proved to play an important part in maintaining body homeostasis and regulating cellular function. However, there are still a lack of studies on the association between malnutrition and Ca deficiency in IBD. This research aimed to investigate the role of Ca for malnutrition in IBD patients. METHODS: We prospectively collected blood samples from 149 patients and utilized inductively coupled plasma mass spectrometry to examine their venous serum trace element concentrations. Logistic regression analyses were used to investigate the association between Ca and malnutrition. Receiver operating characteristic (ROC) curves were generated to calculate the cutoffs for determination of Ca deficiency. RESULTS: Except Ca, the concentrations of the other six trace elements presented no statistical significance between non-malnutrition and malnutrition group. In comparison with the non-malnutrition group, the serum concentration of Ca decreased in the malnutrition group (89.36 vs 87.03 mg/L, p = 0.023). With regard to ROC curve, Ca < 87.21 mg/L showed the best discriminative capability with an area of 0.624 (95% CI: 0.520, 0.727, p = 0.023). Multivariate analyses demonstrated that Ca < 87.21 mg/L (OR = 3.393, 95% CI: 1.524, 7.554, p = 0.003) and age (OR = 0.958, 95% CI: 0.926, 0.990, p = 0.011) were associated with malnutrition risk. Serum Ca levels were significantly lower in the malnutrition group than those in the non-malnutrition group among UC patients, those with severe disease state or the female group. CONCLUSIONS: In patients with IBD, Ca deficiency is an independent factor for high malnutrition risk.
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Calcio , Enfermedades Inflamatorias del Intestino , Desnutrición , Humanos , Femenino , Desnutrición/sangre , Desnutrición/epidemiología , Masculino , Calcio/sangre , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/sangre , Adulto , Persona de Mediana Edad , Estudios Prospectivos , Oligoelementos/deficiencia , Oligoelementos/sangre , Estado Nutricional , Curva ROC , Factores de Riesgo , AncianoRESUMEN
Rationale and objectives: To develop a prognostic nomogram using mammography data and AJCC staging to predict breast cancer survival. Materials and methods: A prognostic nomogram was created using data from 1000 women diagnosed with breast cancer at a medical cancer center in Taiwan between 2011 and 2015. The variables included age at diagnosis (≤60 or > 60 years), mammography purpose (screening or diagnostic), mammography modality (digital mammogram or digital breast tomosynthesis), and the 7th American Joint Committee on Cancer (AJCC) stage. The outcome predicted was breast cancer-related mortality. The nomogram utilized Kaplan-Meier analysis for all subsets and Cox proportional hazards regression analysis for prediction. The nomogram's accuracy was internally validated using the concordance index and receiver operating characteristic (ROC) curve analysis, focusing on 3-year and 5-year survival predictions. Results: Participants' mean age at breast cancer diagnosis was 54 years (SD = 11.2 years). The 1-year, 3-year, and 5-year overall survival (OS) rates were found to be 99.7%, 95.3%, and 91.4%, respectively. The bootstrap-corrected concordance indices indicated the following: nomogram, 0.807 and AJCC, 0.759. A significant difference was observed between the nomogram's area under the curve (AUC) and the AJCC stage in predicting the probability of 5-year survival (p = 0.005). A nomogram, constructed based on mammography and AJCC, demonstrated excellent calibration through internal validation using bootstrapping. Conclusion: The utilization of a nomogram that incorporates mammography data and the AJCC registry data has been demonstrated to be a reliable predictor of breast cancer survival.
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To ensure prolonged functionality of transpiration-driven electrokinetic power generators (TEPGs) in saltwater environments, it is imperative to mitigate salt accumulation. This study presents a salt pathway transpiration-driven electrokinetic power generator (SPTEPG), incorporating MXene, graphene oxide (GO), and carbon nanotubes (CNTs) as active materials, along with cellulose nanofibers (CNF) and poly(vinyl alcohol) (PVA) as aqueous binders and nonwoven fabrics. This unique combination confers exceptional hydrophilicity and enhances the energy generation performance. When tested with deionized water, the SPTEPG achieved a maximum voltage of 0.6 V and a current of 4.2 µA. In simulated seawater conditions, the presence of conductive ions in the solution boosted these values to 0.64 V and 42 µA. The incorporation of the salt pathway mechanism facilitates the return of excess salt deposits to the bulk solution, thus extending the SPTEPG's service life in saltwater environments. This research offers a straightforward yet effective strategy for designing transpiration-driven power generators suitable for saline water applications.
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In recent years, the development of image super-resolution (SR) has explored the capabilities of convolutional neural networks (CNNs). The current research tends to use deeper CNNs to improve performance. However, blindly increasing the depth of the network does not effectively enhance its performance. Moreover, as the network depth increases, more issues arise during the training process, requiring additional training techniques. In this paper, we propose a lightweight image super-resolution reconstruction algorithm (SISR-RFDM) based on the residual feature distillation mechanism (RFDM). Building upon residual blocks, we introduce spatial attention (SA) modules to provide more informative cues for recovering high-frequency details such as image edges and textures. Additionally, the output of each residual block is utilized as hierarchical features for global feature fusion (GFF), enhancing inter-layer information flow and feature reuse. Finally, all these features are fed into the reconstruction module to restore high-quality images. Experimental results demonstrate that our proposed algorithm outperforms other comparative algorithms in terms of both subjective visual effects and objective evaluation quality. The peak signal-to-noise ratio (PSNR) is improved by 0.23 dB, and the structural similarity index (SSIM) reaches 0.9607.
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The rapid development of natural language processing technology and improvements in computer performance in recent years have resulted in the wide-scale development and adoption of human-machine dialogue systems. In this study, the Icc_dialogue model is proposed to enhance the semantic awareness of moods for emotional interactive robots. Equipped with a voice interaction module, emotion calculation is conducted based on model responses, and rules for calculating users' degree of interest are formulated. By evaluating the degree of interest, the system can determine whether it should transition to a new topic to maintain the user's interest. This model can also address issues such as overly purposeful responses and rigid emotional expressions in generated replies. Simultaneously, this study explores topic continuation after answering a question, the construction of dialogue rounds, keyword counting, and the creation of a target text similarity matrix for each text in the dialogue dataset. The matrix is normalized, weights are assigned, and the final text score is calculated. In the text with the highest score, the content of dialogue continuation is determined by calculating a subsequent sentence with the highest similarity. This resolves the issue in which the conversational bot fails to continue dialogue on a topic after answering a question, instead waiting for the user to voluntarily provide more information, resulting in topic interruption. As described in the experimental section, both automatic and manual evaluations were conducted to validate the significant improvement in the mood semantic awareness model's performance in terms of dialogue quality and user experience.
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Robótica , Humanos , Semántica , Comunicación , Lenguaje , EmocionesRESUMEN
Background: Achalasia cardia (AC) is defined as a disorder of esophageal motility whose diagnostic gold standard depends on high-resolution manometry (HRM). The invasiveness of HRM can cause difficulties in diagnosis, treatment, and follow-up for patients with AC. Thus, we aimed to investigate the function of 3D reconstruction and measurement to prove the wide application of this alternative non-invasive approach for AC. Methods: A total of 126 patients with AC and 40 healthy subjects in Tianjin Medical University General Hospital from January 2018 to October 2022 were enrolled in this retrospective study. Chest CT images of these subjects were used to reconstruct the 3D models of the esophagus, stomach, spine, left crus, and right crus. Measurements of esophagus length, volume of esophagus, gastroesophageal insertion angle (His angle), max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, esophagus-spine angle, and spine-lower esophageal sphincter (LES) angle were applied based on the models. Results: Retrocardiac esophagus length, volume of esophagus, max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, thoracic esophagus-spine angle, and spine-LES angle in the AC group were higher than those in the control group (all P values <0.05). Among the three subtypes of AC, thoracic esophagus length, intra-abdominal LES length, volume of esophagus, His angle, esophagus maximum transverse and longitudinal diameter, and thoracic esophagus-spine angle all presented statistical differences (all P values <0.05). Correlation analysis revealed that manometric types were positively associated with His angle [r=0.196; 95% confidence interval (CI): 0.009, 0.372; P=0.028] but negatively associated with volume of esophagus (r=-0.480; 95% CI: -0.639, -0.310; P<0.001), esophagus maximum transverse diameter (r=-0.551; 95% CI: -0.679, -0.400; P<0.001), esophagus maximum longitudinal diameter (r=-0.518; 95% CI: -0.649, -0.366; P<0.001), and thoracic esophagus-spine angle (r=-0.324; 95% CI: -0.479, -0.157; P<0.001). Conclusions: This study successfully presented the differences in esophageal length, volume, thickness, and angles between healthy subjects and different AC subtypes on the basis of 3D reconstruction and measurement. Thus, 3D model and measurement can be regarded as a good support for further research and make a valuable contribution to developing non-invasive approaches for AC management.
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Integrated source analysis and risk assessment of metals facilitate the development of targeted risk management strategies. However, previous studies usually addressed total concentration rather than bioavailability, and consequently overestimated metal risk, especially natural source-related risk. In this study, a source-specific risk assessment was conducted by integrating the source analysis of bioavailable metals in surface sediments. Moreover, risk assessment was performed using two bioavailability-based indices: the total availability risk index (TARI) and a modified index of mean probable effect concentration quotients (mPEC-Q). A representative river watershed in eastern China was selected as the study area. Findings revealed that the total concentrations of Pb, Cu, Zn, Cr, and Ni in the sediments were 1.4-2.2 times higher than the local soil background values. Using a modified community bureau of reference (BCR) sequential extraction procedure, the dominant fraction for Pb, Cu, Zn, and Cr in the studied area was found to be the residual fraction, constituting 53.63-62.44% of the total concentrations. This suggested that a significant portion of the metals potentially originated from natural sources. Nevertheless, the concentration enrichment ratio (CER) indicated that anthropogenic sources contributed significantly, accounting for 67.84-87.68% of bioavailable metals. The positive matrix factorization (PMF) model further identified three different sources of bioavailable metals, with a descending concentration contribution sequence of industrial sources (37.61%), mixed traffic and natural sources (33.17%), and agricultural sources (29.22%). Both the TARI and mPEC-Q index values indicated that the bioavailable metals generally posed a moderate risk, and Ni was the priority pollutant. Industrial sources contributed the most to the total risk, although the contribution from TARI-based assessment (37.27%) was lower than that from the mPEC-Q assessment (46.43%). This study provides an example of the consideration of metal bioavailability in the context of source-specific risk assessments to develop more reasonable management strategies.
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Metales Pesados , Contaminantes Químicos del Agua , Metales Pesados/análisis , Monitoreo del Ambiente , Ríos , Plomo/análisis , Medición de Riesgo , China , Contaminantes Químicos del Agua/análisis , Sedimentos Geológicos/análisis , Cadmio/análisisRESUMEN
As the first isopropanol chiral triazole fungicide, mefentrifluconazole has broad prospects for application. In this study, the stereoselective stability, bioactivity, fate, and biotoxicity were systematically investigated. Our results indicated that the stability of mefentrifluconazole enantiomers differed between environmental media, and they were stable in water and sediment in the dark. The bactericidal activity of R-mefentrifluconazole against the four target pathogens was 4.6-43 times higher than that of S-mefentrifluconazole. In the water-sediment system, S-mefentrifluconazole dissipated faster than R-mefentrifluconazole in water; however, its accumulation capacity was higher than that of R-mefentrifluconazole in sediment and zebrafish. S-Mefentrifluconazole induced more differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in zebrafish than did R-mefentrifluconazole. Multiomics sequencing results showed that S-mefentrifluconazole enhanced the antioxidant, detoxification, immune, and metabolic functions of zebrafish by interacting with related proteins. Based on AlphaFold2 modeling and molecular docking, mefentrifluconazole enantiomers had different binding modes with key target proteins in pathogens and zebrafish, which may be the main reason for the stereoselective differences in bioactivity and biotoxicity. Based on its excellent bioactivity and low biotoxicity, the R-enantiomer can be developed to improve the bioactivity and reduce the risk of mefentrifluconazole.
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Fungicidas Industriales , Pez Cebra , Animales , Simulación del Acoplamiento Molecular , Multiómica , Fungicidas Industriales/química , Fungicidas Industriales/toxicidad , Conducta de Reducción del Riesgo , Estereoisomerismo , AguaRESUMEN
Non-hydraulic root signals (nHRS) are affirmed as a unique positive response to soil drying, and play a crucial role in regulating water use efficiency and yield formation in dryland wheat production. Strigolactones (SLs) can enhance plant drought adaptability. However, the question of whether strigolactones enhance grain yield and water use efficiency by regulating nHRS and antioxidant defense systems in dryland wheat remains unanswered. In this study, pot experiments were conducted to investigate the effects of strigolactones on nHRS, antioxidant defense system, and grain yield and water use efficiency in dryland wheat. The results showed that external application of SLs increased drought-induced abscisic acid (ABA) accumulation and activated an earlier trigger of nHRS at 73.4% field capacity (FC), compared to 68.5% FC in the control group (CK). This phenomenon was mechanically associated with the physiological mediation of SLs. The application of SLs significantly enhanced the activities of leaf antioxidant enzymes, reduced ROS production, and mitigated oxidative damage to lipid membrane. Additionally, root biomass, root length density, and root to shoot ratio were increased under strigolactone treatment. Furthermore, exogenous application of SLs significantly increased grain yield by 34.9% under moderate drought stress. Water use efficiency was also increased by 21.5% and 33.3% under moderate and severe drought conditions respectively, compared to the control group (CK). The results suggested that the application of strigolactones triggered earlier drought-sensing mechanism and improved the antioxidant defense ability, thus enhancing grain yield and water use efficiency in dryland wheat production.
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This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.
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Isquemia Encefálica , FN-kappa B , Ratas , Masculino , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Quinasa I-kappa B/metabolismo , Quinasa I-kappa B/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología , Interleucina-6/genética , Péptido Relacionado con Gen de Calcitonina/farmacología , Ratas Sprague-Dawley , Transducción de Señal , Isquemia Encefálica/tratamiento farmacológico , ComprimidosRESUMEN
Clarifying the molecular mechanisms of cotton aphid resistance to various insecticides is crucial for the long-term safe application of insecticides in chemical control. ATP-binding cassette (ABC) transporters mediate the membrane transport of various substrates (including exogenous substances). Experiments confirmed that ABCB5, ABCF2, and MRP12 contributed to high levels of resistance to spirotetramat, cyantraniliprole, thiamethoxam or imidacloprid. Binding sites of the C2H2 zinc finger transcription factor CF2-II was predicted to be located in the promoters of ABCB5, ABCF2, and MRP12. The expression levels of ABCB5, ABCF2, and MRP12 were significantly upregulated after silencing CF2-II. The results of dual-luciferase reporter assays demonstrated a negative regulatory relationship between CF2-II and ABC transporter promoters. Furthermore, yeast one-hybrid (Y1H) and electrophoresis mobility shift assays (EMSAs) revealed that CF2-II inhibited the expression of ABC transporter genes through interaction with binding sites [ABCF2.p (-1149/-1140) or MRP12.p (-1189/-1181)]. The above results indicated that ABCB5, ABCF2, and MRP12 were negatively regulated by the transcription factor CF2-II, which will help us further understand the mechanism of transcriptional adaption of multi-insecticides resistant related ABC transporters in response to xenobiotics.
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Áfidos , Dedos de Zinc CYS2-HIS2 , Insecticidas , Animales , Insecticidas/farmacología , Resistencia a los Insecticidas/genética , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Factores de Transcripción/metabolismo , Áfidos/genética , Protrombina/metabolismoRESUMEN
Cytochrome P450-mediated metabolism is an important mechanism of insecticide resistance, most studies show upregulated transcript levels of P450s in resistant insect strains. Our previous studies illustrated that some upregulated P450s were associated with cyantraniliprole resistance, and it is more comprehensive to use the tissue specificity of transcriptomes to compare resistant (CyR) and susceptible (SS) strains. In this study, the expression profiles of P450s in a CyR strain compared with a SS strain in remaining carcass or midgut were investigated by RNA sequencing, and candidate genes were selected for functional study. Drosophila melanogaster bioassays suggested that ectopic overexpression of CYP4CK1, CYP6CY5, CYP6CY9, CYP6CY19, CYP6CZ1 and CYP6DA1 in flies was sufficient to confer cyantraniliprole resistance, among which CYP6DA1 was the predominant contributor to resistance (12.24-fold). RNAi suppression of CYP4CK1, CYP6CY5, CYP6CY9 and CYP6DA1 significantly increased CyR aphid sensitivity to cyantraniliprole. The CYP6DA1 promoter had two predicted binding sites for crocodile (CROC), an intron-free ORF with bidirectional transcription yielding CROC (+) and CROC (-). Y1H, RNAi and EMSA found that CROC (-) was a transcription factor directly regulating CYP6DA1 expression. In conclusion, P450 genes contribute to cyantraniliprole resistance, and the transcription factor CROC (-) regulates the expression of CYP6DA1 in A. gossypii.
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Caimanes y Cocodrilos , Áfidos , Insecticidas , Animales , Insecticidas/metabolismo , Caimanes y Cocodrilos/metabolismo , Áfidos/genética , Drosophila melanogaster/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Background: The burden of obesity and chronic disease is increasing in the older US Hispanic/Latino adult population. There is limited evidence on successful weight management strategies as perceived by this population. Assessing barriers and opportunities for weight management using mixed methods is a robust approach to collect in-depth information that can be applied to the development of well-tailored weight management interventions for this population. Objective: The objective of this study was to assess perceived individual, interpersonal, and environmental factors that influence weight management in older Hispanic/Latino adults. Methods: This community-based cross-sectional study included 23 Hispanic/Latino older (>50y) adults with obesity (BMI >30 kg/m2). Perceived barriers and opportunities for weight management were assessed through validated questionnaires and focus groups. Prospectively registered on ClinicalTrials.gov (NCT03978416) on 7 June 2019. Results: In this demographically heterogeneous population, language acculturation was generally low, and the frequency of poor dietary behaviors was high. Participants linked financial strain to lower diet quality, as well as anxiety to uncontrolled eating and food cravings. Social support and trust in healthcare professionals were perceived as priorities for healthy eating. Structural and environmental barriers such as affordability and availability of culturally preferred foods were also identified as influences on food choices and eating behavior. Conclusions: This study revealed opportunities for culturally tailored weight management interventions in older Hispanic/Latino adults with obesity. Clinical Trial Registry Number: NCT03978416 (ClinicalTrials.gov).