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BACKGROUND: Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15-39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. METHODS: Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation. RESULTS: Between 1990 and 2021, the worldwide prevalence of migraine among 15-39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35-39 age group. Notably, female rates consistently exceeded male rates across all age categories. CONCLUSION: The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine.
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Charge mondiale de morbidité , Santé mondiale , Migraines , Humains , Migraines/épidémiologie , Adolescent , Jeune adulte , Adulte , Mâle , Femelle , Charge mondiale de morbidité/tendances , Prévalence , Santé mondiale/statistiques et données numériques , Incidence , Années de vie ajustées sur la qualité , Espérance de vie corrigée de l'incapacité/tendancesRÉSUMÉ
Dechloranes, including dechlorane 602 (Dec 602), dechlorane 603 (Dec 603), dechlorane 604 (Dec 604), dechlorane plus (DP, including syn- and anti-DP) and mirex, were determined in marine food web from Dalian Bay, Northeast China to investigate their occurrence andtrophic transfer. In all organisms, the detection rates were Dec 602 (99%) > mirex (95%) > Dec 603 (92%) > anti-DP (91%) > syn-DP (82%) > Dec 604 (9.6%). The concentrations were 0.92-16 ng/g lipid weight (lw) for mirex, 0.53-2.3 ng/g lw for syn-DP, 1.1-4.5 ng/g lw for anti-DP, 0.19-5.0 ng/g lw for Dec 602, 0.26-1.9 ng/g lw for Dec 603 and 0.020-0.33 ng/g lw for Dec 604. Significant positive relationships (p < 0.0001) were observed between lipid normalized concentrations and trophic levels for mirex (R2 = 0.80) and Dec602 (R2 = 0.82) in food webs, with the calculated TMFs values of 3.09 and 3.39, respectively, indicating the trophic magnification potential of these compounds. For syn-DP, anti-DP, Dec 603 and Dec 604, the similar significant relationships were not found, suggesting that these chemicals do not trophic magnification nor trophic dilution in the food web. With low log KOW values for mirex (7.01) and Dec 602 (8.05), these two compounds have the highest magnifications potentials, while the magnification potential of Dec 603, Dec 604 and DP dramatically decreased because of their extremely big log KOW values (higher than 10). The observed fractional abundance of anti-DP (fanti) ranged of 0.58-0.69, closing to the one in Chinese industrial products, indicating DP isomers had not undergone significant differences of physicochemical or biological process in the studied food web.
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Spinal diseases and frozen shoulder are prevalent health problems in Asian populations. Early assessment and treatment are very important to prevent the disease from getting worse and reduce pain. In the field of computer vision, it is a challenging problem to assess the range of motion. In order to realize efficient, real-time and accurate assessment of the range of motion, an assessment system combining MediaPipe and YOLOv5 technologies was proposed in this study. On this basis, Convolutional Block Attention Module (CBAM) is introduced into the YOLOv5 target detection model, which can enhance the extraction of feature information, suppress background interference, and improve the generalization ability of the model. In order to meet the requirements of large-scale computing, a client/server (C/S) framework structure is adopted. The evaluation results can be obtained quickly after the client uploads the image data, providing a convenient and practical solution. In addition, a game of "Picking Bayberries" was developed as an auxiliary treatment method to provide patients with interesting rehabilitation training.
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Bursite , Amplitude articulaire , Maladies du rachis , Humains , Bursite/physiopathologie , Bursite/thérapie , Bursite/diagnostic , Maladies du rachis/diagnostic , Maladies du rachis/physiopathologie , Maladies du rachis/thérapie , Mâle , Femelle , Adulte , Adulte d'âge moyenRÉSUMÉ
BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.
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Indice de masse corporelle , Exercice physique , Accident vasculaire cérébral , Humains , Mâle , Sujet âgé , Femelle , Accident vasculaire cérébral/épidémiologie , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Charge mondiale de morbidité , Facteurs de risque , Espérance de vie corrigée de l'incapacité , Mode de vie sédentaireRÉSUMÉ
Dissolved black carbon (DBC) is the more photoactive component of dissolved organic matter (DOM) pool, which plays a dual role in the photoconversion of aquatic contaminants, acting as both a photosensitizer and an inhibitor. However, little is known about the more systematic mechanism by which DBC exhibits a dual effect, which is closely related to the structure composition of DBC. In this study, the differences in characteristics of DBC obtained from 300 °C and 500 °C were compared via UV-vis absorption spectrum, Fluorescence excitation emission matrix spectra (3D-EEM), Fourier transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS), and evaluated the promoting and inhibiting effects of DBC on ofloxacin (OFL) photodegradation. It was found that higher pyrolysis temperature reduced the UV absorbance, molecular weight, aromaticity, and phenolics of DBC while increasing the content of quinone/aromatic ketone and humic substances. Photochemical data showed that 3DBC*, 1O2 and ·OH were all participated in the DBC-mediated OFL photodegradation. Wherein, DBC300 (DBCT, where T = pyrolysis temperature) had strong light screening and dynamic quenching effect, but the formation ability of 3DBC*, 1O2 and ·OH was poor, which significantly retarded the photodegradation of OFL. While DBC500 exhibited a slight promotion effect due to its higher formation ability of reactive species and weak light screening effect. Moreover, DBC500 had higher steady-state concentration and (kOFL,3DBCâ) than DBC300, which might be due to the higher contents of quinone/aromatic ketone and the lower contents of phenol in DBC500, thus enhancing the reactivity of 3DBC* and OFL. Our research systematically revealed the trade-off mechanism of DBC on the photodegradation of fluoroquinolones, and provided an important theoretical guidance for the photodegradation of fluoroquinolones under the evolution of DBC composition.
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Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR-Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC.
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Systèmes CRISPR-Cas , Carcinome hépatocellulaire , Tumeurs du foie , Nanocapsules , Microenvironnement tumoral , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/immunologie , Carcinome hépatocellulaire/thérapie , Microenvironnement tumoral/immunologie , Microenvironnement tumoral/génétique , Tumeurs du foie/génétique , Tumeurs du foie/immunologie , Tumeurs du foie/thérapie , Tumeurs du foie/anatomopathologie , Systèmes CRISPR-Cas/génétique , Souris , Humains , Animaux , Immunothérapie/méthodes , Modèles animaux de maladie humaine , Édition de gène/méthodes , Lignée cellulaire tumoraleRÉSUMÉ
Lattice distortions are intrinsic features of all solid solution alloys associated with varying atomic radii; this phenomenon facilitates the formation of single-phase solid solutions. Using high-entropy alloys (HEAs), as an example, we investigate the influence of variations in inter-atomic separations for stabilizing and controlling their structural, mechanical, and thermodynamic properties. This is done through a combination of statistical mechanics analysis and molecular dynamics simulations on simplified 2D systems, as well as a 3D crystals with harmonic and anharmonic inter-atomic bonds with varying natural inter-atomic separations. We demonstrate that the impact of this inter-atomic length disorder (representing static lattice distortion) and temperature fluctuations (representing dynamic lattice distortion) on fundamental and universal thermodynamic, structural, and elastic characteristics are similar and can be unified through effective temperature; i.e. a scaling law for HEAs that establishes a relationship between these factors. This scaling law reveals that different HEAs (i.e. varying degrees of local lattice distortions) collapse onto a single curve when plotted against the effective temperature. We demonstrate that lattice distortion significantly enhances the stability of solid solution alloys (relative to phase separation or ordering by effectively increasing the temperature of the system; this stabilization effect is particularly pronounced in HEAs).
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BACKGROUND: Cockroaches are widely acknowledged as significant vectors of pathogenic microorganisms. The Periplaneta fuliginosa densovirus (PfDNV) infects the smoky-brown cockroach P. fuliginosa and causes host mortality, which identifies the PfDNV as a species-specific and environmentally friendly biopesticide. However, although the biochemical characterization of PfDNV has been extensively studied, the immune response against PfDNV remains largely unclear. RESULTS: Here, we investigated the replication of PfDNV and its associated pathological phenotype in the foregut and hindgut. Consequently, we dissected and performed transcriptome sequencing on the foregut, midgut, and hindgut separately. We revealed the up-regulation of immune response signaling pathway c-Jun N-terminal kinase (JNK) and apoptosis in response to viral infection. Furthermore, knockdown of the JNK upstream gene Ben resulted in a decrease in virus titer and delayed host mortality. CONCLUSION: Taken together, our findings provide evidence that the Ben-JNK signaling plays a crucial role in PfDNV infection, leading to excessive apoptosis in intestinal tissues and ultimately resulting in the death of the host. Our results indicated that the host response to PfDNV fosters viral infection, thereby increasing host lethality. This underscores the potential of PfDNV as a viable, environmentally friendly biopesticide. © 2024 Society of Chemical Industry.
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Densovirus , Periplaneta , Animaux , Periplaneta/virologie , Periplaneta/physiologie , Periplaneta/génétique , Densovirus/physiologie , Densovirus/génétique , Protéines d'insecte/métabolisme , Protéines d'insecte/génétique , Système de signalisation des MAP kinases , Apoptose , Transduction du signalRÉSUMÉ
Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) represent an effective method for the remediation of antibiotic-contaminated soils. In this study, a natural pyrite-biochar composite material (FBCx) was developed, demonstrating superior activation performance and achieving a 76% removal rate of SMX from soil within 120 min. There existed different degradation mechanisms for SMX in aqueous and soil solutions, respectively. The production of 1O2 and inherent active species produced by soil slurry played an important role in the degradation process. The combination of electron paramagnetic resonance (EPR) and free radical probe experiments confirmed the presence of free radical transformation processes in soil. Wherein, the·OH and SO4·- generated in soil slurry did not directly involve in the degradation process, but rather preferentially reacted with soil organic matter (SOM) to form alkyl-like radicals (R·), thereby maintaining a high concentration of reactive species in the system. Furthermore, germination and growth promotion of mung bean seeds observed in the toxicity test indicated the environmental compatibility of this remediation method. This study revealed the influence mechanism of SOM in the remediation process of contaminated soil comprehensively, which possessed enormous potential for application in practical environments.
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Purpose: This study aimed to examine the influence of unintended facet arthrodesis on the therapeutic effectiveness of the dynamic neutralization system (Dynesys). Methods: This retrospective study enrolled consecutive patients who underwent posterior decompression and dynamic stabilization for lumbar spondylosis or spinal stenosis. Follow-up assessments included lumbar radiography, lumbar vertebral computerized tomography (CT), visual analog scale (VAS), and Oswestry disability index (ODI). Patients were classified into the facet fusion and non-fusion groups. The differences in the VAS scores for back pain and leg pain, ODI, intervertebral range of motion (ROM) at the surgical segments, and upper adjacent segments were assessed before and after treatment. Results: A total of 49 patients (29 males and 20 females) aged 31-65 years were enrolled and followed-up for over 40 months. Among the patients, 16 (32.7%) experienced unintended facet arthrodesis and were assigned to the fusion group, whereas the remaining patients were assigned to the non-fusion group. There was a significant increase in the incidence of facet arthrodesis in the surgical segments over time post-surgery (χ2 = 6.2, p < 0.05). The ROM of the surgical and upper adjacent segments, VAS scores for back pain and leg pain, and ODI were all significantly different before and after the operation (p < 0.05), but not between the fusion and non-fusion groups (p > 0.05). Conclusion: Although unintended facet arthrodesis is common after Dynesys procedure, the presence of facet arthrodesis does not significantly affect the efficacy of Dynesys in treating lumbar degenerative diseases.
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BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease causing central nervous system demyelination, often associated with depression. Current treatments for MS do not effectively address both physical disability and depression. Roflumilast, a phosphodiesterase-4 inhibitor with anti-inflammatory properties, has shown promise for autoimmune diseases. METHODS: We used an experimental autoimmune encephalomyelitis (EAE) rat model to study roflumilast's effects. Motor dysfunction and depression symptoms were assessed, and histopathological analysis evaluated its anti-inflammatory properties. Flow cytometry examined the drug's impact on brain microglia. TNF-α, IL-1ß, and IL-6 levels in hippocampal tissue were assessed using ELISA kits. RESULTS: Roflumilast improved motor dysfunction and depression symptoms in EAE rats. Histopathological analysis revealed reduced inflammation, demyelination, and axonal loss in the spinal cord. Roflumilast suppressed microglial cell activation and conversion to pro-inflammatory M1-type cells. Flow cytometry showed roflumilast inhibited inflammatory marker expression in microglia and their activation in the hippocampus. IL-6 was identified as a roflumilast target for suppressing hippocampal inflammation. LIMITATIONS: This study used an animal model and did not assess long-term or potential side effects of roflumilast treatment. CONCLUSIONS: Roflumilast holds promise as a treatment for depression and motor impairment in MS. Its anti-inflammatory properties, reducing inflammation and inhibiting microglial activation, suggest its potential for MS therapy. However, further research is needed to evaluate long-term effects and safety in MS patients.
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Aminopyridines , Benzamides , Encéphalomyélite auto-immune expérimentale , Sclérose en plaques , Humains , Rats , Animaux , Souris , Sclérose en plaques/traitement médicamenteux , Dépression/traitement médicamenteux , Maladies neuro-inflammatoires , Interleukine-6 , Encéphalomyélite auto-immune expérimentale/traitement médicamenteux , Encéphalomyélite auto-immune expérimentale/anatomopathologie , Inflammation/métabolisme , Anti-inflammatoires/usage thérapeutique , Souris de lignée C57BL , CyclopropanesRÉSUMÉ
Dissolved black carbon (DBC) has high photoactivity, which plays an important role in contaminants photodegradation. However, it is unclear how pyrolysis temperatures would affect the composition and photo-reactivity of DBC at the molecular level. Herein, we combined complementary techniques to study the characteristics of DBC pyrolyzed at 200 - 500 â, as well as the photoproduction of reactive species and the photodegradation of tetracycline (TC). Bulk composition characterization found that condensed aromatic carbonyl compounds (ConAC) with narrow molecular weights in DBC experienced an increase from 200 to 500 °C, which enhanced the photoproduction of 3DBC*,1O2, and ·OH. Molecular-level data suggested that 3DBC* and 1O2 were both related to the same DBC compounds. Comparatively, the patterns for ·OH were less pronounced, implying its precursor was not 3DBC* and had more complexity. Plentiful CHOx species of ConAC in DBC400 and DBC500 (DBCT, where T = pyrolysis temperature) accelerated the generation of 3DBC* and 1O2, enhancing the photodegradation of TC, and mainly triplet states of quinones reacted with TC. In contrast, DBC200 and DBC300 exhibited inhibition since massive CHOx species in lignin-like reduced 3TC* to TC. Our data revealed the diverse photochemical behavior mechanisms of DBC pyrolyzed at 200 - 500 â at the molecular level and the implications for aquatic contaminants photochemistry.
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Pyrolyse , Suie , Température , Photolyse , Analyse spectrale , Suie/analyse , Suie/composition chimique , Antibactériens , Tétracycline , CarboneRÉSUMÉ
A prolonged second stage of vaginal delivery increases the risk of shoulder dystocia, unnecessary episiotomies and cesarean sections. However, no standardized method has been proposed to tackle this issue. The effects of pelvic floor myofascial manipulation intervention during the second stage of labor in primiparas and its prognostic value in neonatal postpartum outcomes remain unknown. In the present study, a total of 60 primiparas who were expecting a vaginal delivery in the Second Affiliated Hospital of Hainan Medical College (Haikou, China) between October 2021 and January 2022 were selected. These women were randomly assigned to a control group (standard intrapartum care) or an experimental group (pelvic floor myofascial manipulation for 15-20 min during the second stage of labor along with standard intrapartum care) using a random number table, with 28 patients in each group. There was no significant difference in age, gestational time or body mass index between the two groups before delivery, indicating that the baseline data were comparable. The second stage of labor duration, forced breath-holding time and postpartum hemorrhage volume in the experimental group were significantly lower than those in the control group. The pain visual analog scale scores, fatigue scores and neonatal Apgar scores in the experimental group were also significantly lower than those in the control group. The rate of episiotomy in the experimental group was lower than that in the control group, but the difference was not statistically significant. In conclusion, pelvic floor myofascial manipulation intervention during the second stage of labor for primiparas with vaginal delivery can reduce the duration of the second stage of labor, the amount of bleeding during labor and the pain during labor. Meanwhile, it has the potential to improve neonatal outcomes.
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Existing model evaluation tools mainly focus on evaluating classification models, leaving a gap in evaluating more complex models, such as object detection. In this paper, we develop an open-source visual analysis tool, Uni-Evaluator, to support a unified model evaluation for classification, object detection, and instance segmentation in computer vision. The key idea behind our method is to formulate both discrete and continuous predictions in different tasks as unified probability distributions. Based on these distributions, we develop 1) a matrix-based visualization to provide an overview of model performance; 2) a table visualization to identify the problematic data subsets where the model performs poorly; 3) a grid visualization to display the samples of interest. These visualizations work together to facilitate the model evaluation from a global overview to individual samples. Two case studies demonstrate the effectiveness of Uni-Evaluator in evaluating model performance and making informed improvements.
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MicroRNAs (miRNAs) are an essential type of small molecule RNAs that play significant regulatory roles in organisms. Recent studies have demonstrated that small open reading frames (sORFs) harbored in primary miRNAs (pri-miRNAs) can encode small peptides, known as miPEPs. Plant miPEPs can increase the abundance and activity of cognate miRNAs by promoting the transcription of their corresponding pri-miRNAs, thereby modulating plant traits. Biological experiments are the most effective way to accurately identify miPEPs; however, they are time-consuming and expensive. Hence, an efficient computational method for the identification of miPEPs on a large scale is highly desirable. Up to now, there have been no specialized computational tools for identifying miPEPs. In this work, a novel predictor named miPEPPred-FRL based on an adaptive feature representation learning framework that consists of the feature transformation module and the cascade architecture has been proposed. The feature transformation module integrating a newly designed feature selection method and classifier selection rule is developed to convert sequence-based features into primary class and probabilistic features, which are then fed into the improved cascade architecture to obtain more stable and discriminative augmented features. Finally, the augmented features are utilized to construct the final predictor. Cross-validation experiments illustrate that the novel feature selection method and classifier selection rule contribute to boosting the feature representation ability of the framework. Furthermore, the high accuracy of miPEPPred-FRL on independent testing data suggests that it is a trustworthy and valuable tool for the identification of miPEPs.
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microARN , microARN/composition chimique , Plantes , Peptides , Biologie informatique/méthodesRÉSUMÉ
Sorafenib, a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), has been shown to be a potent ferroptosis inducer in HCC. However, we found that there was a lower level of ferroptosis in sorafenib-resistant HCC samples than in sorafenib-sensitive HCC samples, suggesting that sorafenib resistance in HCC may be a result of ferroptosis suppression. Recent reports have shown that long noncoding RNAs (lncRNAs) are involved in programmed cell death (PCD), including apoptosis and ferroptosis. This study aimed to investigate the roles and underlying molecular mechanisms of lncRNAs in sorafenib-induced ferroptosis in HCC cells. Using lncRNA sequencing, we identified a ferroptosis-related lncRNA, URB1-antisense RNA 1 (AS1), which was highly expressed in sorafenib-resistant HCC samples and predicted poor survival in HCC. Furthermore, URB1-AS1 mitigates sorafenib-induced ferroptosis by inducing ferritin phase separation and reducing the cellular free iron content. Hypoxia inducible factor (HIF)-1α was identified as a key factor promoting URB1-AS1 expression in sorafenib-resistant HCC cells. Notably, we found that specifically inhibiting the expression of URB1-AS1 with N-acetylgalactosamine (GalNAc)-small interfering (si)URB1-AS1 successfully enhanced the sensitivity of HCC cells to sorafenib in an in vivo tumor model. Our study uncovered a critical role for URB1-AS1 in the repression of ferroptosis, suggesting URB1-AS1 targeting may represent a potential approach to overcome sorafenib resistance in HCC.
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Carcinome hépatocellulaire , Ferroptose , Tumeurs du foie , microARN , ARN long non codant , Humains , Carcinome hépatocellulaire/traitement médicamenteux , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/métabolisme , Sorafénib/pharmacologie , ARN long non codant/génétique , ARN long non codant/métabolisme , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/génétique , Tumeurs du foie/métabolisme , ARN antisens , Ferritines/métabolisme , microARN/génétique , Lignée cellulaire tumorale , Petit ARN interférent/génétique , Prolifération cellulaire , Régulation de l'expression des gènes tumoraux , Protéines nucléaires/génétiqueRÉSUMÉ
Bioaccumulation factor (BAF) of pollutants is an important parameter for evaluating their bioaccumulation potential and an important indicator for evaluating their environmental risks. However, little study exits on the BAF of novel brominated flame retardants (NBFRs). The present study determined 17 NBFRs in 24 water samples in dissolved phase and 93 crucian carp samples collected from an electronic waste recycling site in northern China, in order to examine their contamination, distribution and bioaccumulation. The results showed that the targeted NBFRs were widely detectable in the dissolved phase and crucian carps. In dissolved phase, allyl 2,4,6-tribromophenyl ether (ATE) had the highest detectable rate (100%) and concentration (mean: 1.3 ± 0.62 ng/L), but in crucian carp, hexachlorocyclopentenyl-dibromocyclooctane (HCDBCO) was the one with the highest detectable rate (89%) and concentration (mean: 16 ± 9.2 ng/g wet weight (ww)) among all 17 NBFRs. The discharge and water solubility of NBFRs determined their concentration in the dissolved phase, while the concentration of NBFRs in crucian carp was the results of their discharge and food exposure. The estimated BAFs exceeded 5000 L/kg for petabromoethylbenzene (PBEB), pentabromotoluene (PBT), HCDBCO, pentabromobenzyl acrylate (PBBA), 1,2,3,4,5-pentabromobenzene (PBBZ), 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE), hexabromobenzene (HBBZ), and α-1,2,5,6-tetrabromocyclooctane (α-TBCO), suggesting that these compounds were above the hazard standard of bioaccumulation. Although the BAFs of 2,3,5,6-tetrabromo-p-xylene (p-TBX), 1,2-bis(2,4,6-tribromophenoxy)-ethane (BTBPE), α-/ß-tetrabromoethylcyclohexane (α-/ß-TBECH) and ATE were less than 5000, the potential of bioaccumulation cannot be ignored. The log BAF of tested NBFRs showed a pattern of first increasing and then decreasing with the increase of log KOW, the water solubility of NBFRs, the exposure to fish, the uptake and depuration of fish were the key factor to this pattern. To our knowledge, the BAF values of the most of NBFRs calculated in this study were not reported in the published work previously.
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Carpes (poisson) , Déchets électroniques , Ignifuges , Animaux , Poisson rouge , Ignifuges/analyse , Bioaccumulation , Surveillance de l'environnement/méthodes , Éthers de polyhalogénophényle/analyse , EauRÉSUMÉ
Antimicrobial peptides (AMPs) play a crucial role in plant immune regulation, growth and development stages, which have attracted significant attentions in recent years. As the wet-lab experiments are laborious and cost-prohibitive, it is indispensable to develop computational methods to discover novel plant AMPs accurately. In this study, we presented a hierarchical evolutionary ensemble framework, named PAMPred, which consisted of a multi-level heterogeneous architecture to identify plant AMPs. Specifically, to address the existing class imbalance problem, a cluster-based resampling method was adopted to build multiple balanced subsets. Then, several peptide features including sequence information-based and physicochemical properties-based features were fed into the different types of basic learners to increase the ensemble diversity. For boosting the predictive capability of PAMPred, the improved particle swarm optimization (PSO) algorithm and dynamic ensemble pruning strategy were used to optimize the weights at different levels adaptively. Furthermore, extensive ten-fold cross-validation and independent testing experimental results demonstrated that PAMPred achieved excellent prediction performance and generalization ability, and outperformed the state-of-the-art methods. It also indicated that the proposed method could serve as an effective auxiliary tool to identify plant AMPs, which would be conducive to explore the immune regulatory mechanism of plants.
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As a pivotal node in modulating various cell behaviors, Rho-associated kinase-1 (ROCK1) has attracted significant attention as a promising therapeutic target in a variety of diseases. Benzamide has been widely reported as a ROCK1 inhibitors in recent years. To better understand its pharmacological properties and to explore its potential inhibitors, a series of ROCK1 inhibitors derived from N-methyl-4-(4-pyrazolidinyl) benzamides (MPBs) were investigated by using three-dimensional quantitative structure-activity relationship (3D-QSAR) models, pharmacophore models, molecular docking, and molecular dynamics (MD) simulation. The comparative Molecular Field Analysis (CoMFA) model (q2 = 0.616, R2 = 0.972, ONC = 4, and r2pred = 0.983) and the best Comparative Molecular Similarity Indices Analysis (CoMSIA) model (q2= 0.740, R2 = 0.982, ONC = 6, and r2pred = 0.824) exhibited reliable predictability with satisfactory validation parameters. In the subsequent virtual screening, VS03 and VS05 were identified to have superior predicted activities and higher docking scores, meanwhile they demonstrated to be reasonably stable in the binding pocket through MD simulations. These results provide a significant theoretical direction for the rational design and development of novel ROCK1 inhibitors.Communicated by Ramaswamy H. Sarma.
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Rheumatoid arthritis (RA) is a chronic autoimmune disorder that can give rise to joint swelling and inflammation, potentially affecting the entire body, closely linked to the state of T cells. The T-cell activation Rho GTPase activating protein (TAGAP) is associated with many autoimmune diseases including RA and is directly linked to the differentiation of Th17 cells. The present study intends to investigate the influence of TAGAP on the RA progression and its mechanism to empower new treatments for RA. A collagen-induced-arthritis (CIA) rat model was constructed, as well as the extraction of CD4+ T cells. RT-qPCR, H&E staining and safranin O/fast green staining revealed that TAGAP interference reduced TAGAP production in the ankle joint of CIA rats, and joint inflammation and swelling were alleviated, which reveals that TAGAP interference reduces synovial inflammation and cartilage erosion in the rat ankle joint. Expression of inflammatory factors (TNF-α, IL-1ß, and IL-17) revealed that TAGAP interference suppressed the inflammatory response. Expression of pro-inflammatory cytokines, matrix-degrading enzymes, and anti-inflammatory cytokines at the mRNA level was detected by RT-qPCR and revealed that TAGAP interference contributed to the remission of RA. Mechanistically, TAGAP interference caused a significant decrease in the levels of RhoA and NLRP3. Assessment of Th17/Treg levels by flow cytometry revealed that TAGAP promotes Th17 cells differentiation and inhibits Treg cells differentiation in vitro and in vivo. In conclusion, TAGAP interference may decrease the differentiation of Th17 cells by suppressing the expression of RhoA and NLRP3 to slow down the RA progression.