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Metastasis is the major culprit of treatment failure in nasopharyngeal carcinoma (NPC). Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2), a core circadian gene, plays a crucial role in the development of various tumors. Nevertheless, the biological role and mechanism of ARNTL2 are not fully elucidated in NPC. In this study, ARNTL2 expression was significantly upregulated in NPC tissues and cells. Overexpression of ARNTL2 facilitated NPC cell migration and invasion abilities, while inhibition of ARNTL2 in similarly treated cells blunted migration and invasion abilities in vitro. Consistently, in vivo xenograft tumor models revealed that ARNTL2 silencing reduced nude mice inguinal lymph node and lung metastases, as well as tumor growth. Mechanistically, ARNTL2 negatively regulated the transcription expression of AMOTL2 by directly binding to the AMOTL2 promoter, thus reducing the recruitment and stabilization of AMOTL2 to LATS1/2 kinases, which strengthened YAP nuclear translocation by suppressing LATS-dependent YAP phosphorylation. Inhibition of AMOTL2 counteracted the effects of ARNTL2 knockdown on NPC cell migration and invasion abilities. These findings suggest that ARNTL2 may be a promising therapeutic target to combat NPC metastasis and further supports the crucial roles of circadian genes in cancer development.
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Factores de Transcripción ARNTL , Proteínas Adaptadoras Transductoras de Señales , Angiomotinas , Movimiento Celular , Ratones Desnudos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Invasividad Neoplásica , Factores de Transcripción , Proteínas Señalizadoras YAP , Animales , Femenino , Humanos , Masculino , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB C , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/metabolismo , Metástasis de la Neoplasia , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Señalizadoras YAP/metabolismoRESUMEN
In multistate non-Hermitian systems, higher-order exceptional points and exotic phenomena with no analogues in two-level systems arise. A paradigm is the exceptional nexus (EX), a third-order EP as the cusp singularity of exceptional arcs (EAs), that has a hybrid topological nature. Using atomic Bose-Einstein condensates to implement a dissipative three-state system, we experimentally realize an EX within a two-parameter space, despite the absence of symmetry. The engineered dissipation exhibits density dependence due to the collective atomic response to resonant light. Based on extensive analysis of the system's decay dynamics, we demonstrate the formation of an EX from the coalescence of two EAs with distinct geometries. These structures arise from the different roles played by dissipation in the strong coupling limit and quantum Zeno regime. Our Letter paves the way for exploring higher-order exceptional physics in the many-body setting of ultracold atoms.
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Video action recognition based on skeleton nodes is a highlighted issue in the computer vision field. In real application scenarios, the large number of skeleton nodes and behavior occlusion problems between individuals seriously affect recognition speed and accuracy. Therefore, we proposed a lightweight multi-stream feature cross-fusion (L-MSFCF) model to recognize abnormal behaviors such as fighting, vicious kicking, climbing over the wall, et al., which could obviously improve recognition speed based on lightweight skeleton node calculation, and improve recognition accuracy based on occluded skeleton node prediction analysis in order to effectively solve the behavior occlusion problem. The experiments show that our proposed All-MSFCF model has a video action recognition average accuracy rate of 92.7% for eight kinds of abnormal behavior recognition. Although our proposed lightweight L-MSFCF model has an 87.3% average accuracy rate, its average recognition speed is 62.7% higher than the full-skeleton recognition model, which is more suitable for solving real-time tracing problems. Moreover, our proposed Trajectory Prediction Tracking (TPT) model could real-time predict the moving positions based on the dynamically selected core skeleton node calculation, especially for the short-term prediction within 15 frames and 30 frames that have lower average loss errors.
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This study aims to decipher the mechanism of sinomenine in inhibiting platelet-derived growth factor/platelet-derived growth factor receptor(PDGF/PDGFR) signaling pathway in rheumatoid arthritis-fibroblast-like synoviocyte(RA-FLS) migration induced by neutrophil extracellular traps(NETs). RA-FLS was isolated from the synovial tissue of 3 RA patients and cultured. NETs were extracted from the peripheral venous blood of 4 RA patients and 4 healthy control(HC). RA-FLS was classified into control group, HC-NETs group, RA-NETs group, RA-NETs+sinomenine group and RA-NETs+sinomenine+CP-673451 group. RNA-sequencing(RNA-seq) was conducted to identify the differentially expressed genes between HC-NETs and RA-NETs groups. Sangerbox was used to perform the Gene Ontology(GO) function and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape was employed to build the protein-protein interaction(PPI) network. AutoDock Vina and PyMOL were used for molecular docking of sinomenine with PDGFß and PDGFRß. The cell proliferation and migration were determined by the cell counting kit-8(CCK-8) and cell scratch assay, respectively. Western blot was employed to determine the protein level of PDGFRß. Real-time quantitative polymerase chain reaction(RT-qPCR) was carried out to determine the mRNA levels of matrix metalloproteinases(MMPs). The results revealed that neutrophils in RA patients were more likely to produce NETs. Compared with HC-NETs group, RA-NETs group showed up-regulated expression of PDGFß and PDGFRß. Compared with control group, RA-NETs group showed increased cell proliferation and migration and up-regulated protein level of PDGFRß and mRNA levels of PDGFß, PDGFRß, MMP1, MMP3, and MMP9(P<0.05). Compared with RA-NETs group, RA-NETs+sinomenine group presented decreased cell proliferation and migration and down-regulated protein and mRNA level of PDGFRß and mRNA levels of MMP1, MMP3, and MMP9(P<0.05). Compared with RA-NETs+sinomenine group, the proliferation ability of RA-NETs+sinomenine+CP-673451 group decreased(P<0.05). The findings prove that sinomenine reduces the RA-NETs-induced RA-FLS migration by inhibiting PDGF/PDGFR signaling pathway, thus mitigating RA.
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Artritis Reumatoide , Movimiento Celular , Morfinanos , Factor de Crecimiento Derivado de Plaquetas , Transducción de Señal , Sinoviocitos , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Movimiento Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Morfinanos/farmacología , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptores del Factor de Crecimiento Derivado de Plaquetas/genética , Receptores del Factor de Crecimiento Derivado de Plaquetas/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Masculino , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismoRESUMEN
With the acceleration of urbanisation, urban areas are subject to the combined effects of the accumulation of various natural factors, such as changes in temperature leading to the thermal expansion or contraction of surface materials (rock, soil, etc.) and changes in precipitation and humidity leading to an increase in the self-weight of soil due to the infiltration of water along the cracks or pores in the ground. Therefore, the subsidence of urban areas has now become a serious geological disaster phenomenon. However, the use of traditional neural network prediction models has limitations when examining the causal relationships between time series surface deformation data and multiple influencing factors and when applying multiple influencing factors for predictive analyses. To this end, Sentinel-1A data from March 2017 to February 2023 were used as the data source in this paper, based on time series deformation data acquired using the small baseline subset interferometric synthetic aperture radar (SBAS-InSAR) technique. A sparrow search algorithm-convolutional neural network-long short-term memory (SSA-CNN-LSTM) neural network prediction model was built. The six factors of temperature, humidity, precipitation, and ground temperature at three different depths below the surface (5 cm, 10 cm, and 15 cm) were taken as the input of the model, and the surface deformation data were taken as the output of the neural network model. The correlation between the spatial and temporal evolution characteristics of the ground subsidence in urban areas and various influencing factors was analysed using grey correlation analysis, which proved that these six factors contribute to some extent to the deformation of the urban surface. The main urban area of Hohhot City, Inner Mongolia Autonomous Region, was used as the study area. In order to verify the efficacy of this neural network prediction model, the prediction effects of the multilayer perceptron (MLP), backpropagation (BP), and SSA-CNN-LSTM models were compared and analysed, with the values of the correlation coefficients of the feature points of A1, B1, and C1 being in the range of 0.92, 0.83, and 0.93, respectively. The results show that compared with the traditional MLP and BP neural network models, the SSA-CNN-LSTM model achieves a higher performance in predicting time series surface deformation data in urban areas, which provides new ideas and methods for this area of research.
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BACKGROUND: Endoscopic mucosal resection (EMR) appears to be a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. To assess the effectiveness and safety of EMR for removing SSPs ≥ 10 mm, we conducted this systematic review and meta-analysis. METHODS: We conducted a thorough search of Embase, PubMed, Cochrane, and Web of Science databases for relevant studies reporting on EMR of SSPs ≥ 10 mm, up until December 2023. Our primary endpoints of interest were rates of technical success, residual SSPs, and adverse events (AE). RESULTS: Our search identified 426 articles, of which 14 studies with 2262 SSPs were included for analysis. The rates of technical success, AEs, and residual SSPs were 100%, 2.0%, and 3.1%, respectively. Subgroup analysis showed that the technical success rates were the same for polyps 10-19 and 20 mm, and en-bloc and piecemeal resection. Residual SSPs rates were similar in en-bloc and piecemeal resection, but much lower in cold EMR (1.0% vs. 4.2%, P = 0.034). AEs rates were reduced in cold EMR compared to hot EMR (0% vs. 2.9%, P = 0.168), in polyps 10-19 mm compared to 20 mm (0% vs. 4.1%, P = 0.255), and in piecemeal resection compared to en-bloc (0% vs. 0.7%, P = 0.169). CONCLUSIONS: EMR is an effective and safe technique for removing SSPs ≥ 10 mm. The therapeutic effect of cold EMR is superior to that of hot EMR, with a lower incidence of adverse effects. PROSPERO REGISTRATION NUMBER: CRD42023388959.
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Pólipos del Colon , Resección Endoscópica de la Mucosa , Humanos , Resección Endoscópica de la Mucosa/métodos , Pólipos del Colon/cirugía , Pólipos del Colon/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Leucine (Leu) is an essential amino acid that facilitates skeletal muscle satellite cell differentiation, yet its mechanism remains underexplored. Sestrin2 (SESN2) serves as a Leu sensor, binding directly to Leu, while ribophorin II (RPN2) acts as a signaling factor in multiple pathways. This study aimed to elucidate Leu's impact on mouse C2C12 cell differentiation and skeletal muscle injury repair by modulating RPN2 expression through SESN2, offering a theoretical foundation for clinical skeletal muscle injury prevention and treatment. RESULTS: Leu addition promoted C2C12 cell differentiation compared to the control, enhancing early differentiation via myogenic determinant (MYOD) up-regulation. Sequencing revealed SESN2 binding to and interacting with RPN2. RPN2 overexpression up-regulated MYOD, myogenin and myosin heavy chain 2, concurrently decreased p-GSK3ß and increased nuclear ß-catenin. Conversely, RPN2 knockdown yielded opposite results. Combining RPN2 knockdown with Leu rescued increased p-GSK3ß and decreased nuclear ß-catenin compared to Leu absence. Hematoxylin and eosin staining results showed that Leu addition accelerated mouse muscle damage repair, up-regulating Pax7, MYOD and RPN2 in the cytoplasm, and nuclear ß-catenin, confirming that the role of Leu in muscle injury repair was consistent with the results for C2C12 cells. CONCLUSION: Leu, bound with SESN2, up-regulated RPN2 expression, activated the GSK3ß/ß-catenin pathway, enhanced C2C12 differentiation and expedited skeletal muscle damage repair. © 2024 Society of Chemical Industry.
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Diferenciación Celular , Glucógeno Sintasa Quinasa 3 beta , Leucina , Transducción de Señal , beta Catenina , Animales , Ratones , beta Catenina/metabolismo , beta Catenina/genética , Línea Celular , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Leucina/metabolismo , Leucina/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/citología , Mioblastos/metabolismo , Mioblastos/citología , Proteína MioD/metabolismo , Proteína MioD/genética , Miogenina/metabolismo , Miogenina/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , SestrinasRESUMEN
BACKGROUND: Non-anatomical factors significantly affect treatment guidance and prognostic prediction in nasopharyngeal carcinoma (NPC) patients. Here, we developed a novel survival model by combining conventional TNM staging and serological indicators. METHODS: We retrospectively enrolled 10,914 eligible patients with nonmetastatic NPC over 2009-2017 and randomly divided them into training (n = 7672) and validation (n = 3242) cohorts. The new staging system was constructed based on T category, N category, and pretreatment serological markers by using recursive partitioning analysis (RPA). RESULTS: In multivariate Cox analysis, pretreatment cell-free Epstein-Barr virus (cfEBV) DNA levels of >2000 copies/mL [HROS (95 % CI) = 1.78 (1.57-2.02)], elevated lactate dehydrogenase (LDH) levels [HROS (95 % CI) = 1.64 (1.41-1.92)], and C-reactive protein-to-albumin ratio (CAR) of >0.04 [HROS (95 % CI) = 1.20 (1.07-1.34)] were associated with negative prognosis (all P < 0.05). Through RPA, we stratified patients into four risk groups: RPA I (n = 3209), RPA II (n = 2063), RPA III (n = 1263), and RPA IV (n = 1137), with 5-year overall survival (OS) rates of 93.2 %, 86.0 %, 80.6 %, and 71.9 % (all P < 0.001), respectively. Compared with the TNM staging system (eighth edition), RPA risk grouping demonstrated higher prognostic prediction efficacy in the training [area under the curve (AUC) = 0.661 vs. 0.631, P < 0.001] and validation (AUC = 0.687 vs. 0.654, P = 0.001) cohorts. Furthermore, our model could distinguish sensitive patients suitable for induction chemotherapy well. CONCLUSION: Our novel RPA staging model outperformed the current TNM staging system in prognostic prediction and clinical decision-making. We recommend incorporating cfEBV DNA, LDH, and CAR into the TNM staging system.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Estadificación de Neoplasias , Carcinoma Nasofaríngeo/patología , Estudios Retrospectivos , Herpesvirus Humano 4/genética , Pronóstico , Neoplasias Nasofaríngeas/patología , ADNRESUMEN
Neutrophilic asthma is a persistent and severe inflammatory lung disease characterized by neutrophil activation and the mechanisms of which are not completely elucidated. Ubiquitin D (UBD) is a ubiquitin-like modifier participating in infections, immune responses, and tumorigenesis, while whether UBD involves in neutrophilic asthma needs further study. In this study, we initially found that UBD expression was significantly elevated and interleukin 17 (IL-17) signaling was enriched in the endobronchial biopsies of severe asthma along with neutrophils increasing by bioinformatics analysis. We further confirmed that UBD was upregulated in the lung tissues of neutrophilic asthma mouse model. UBD overexpression promoted IL-17 signaling activation. Knockdown of UBD suppressed the activation of IL-17 signaling. UBD interacted with TRAF2 and reduced the total and the K48-linked ubiquitination of TRAF2. However, IL-17 A stimulation increased both the total and the K48-linked ubiquitination of TRAF2. Together, these findings indicated that UBD was upregulated and played a critical role in IL-17 signaling which contributed to a better understanding of the complex mechanisms in neutrophilic asthma.
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Asma , Interleucina-17 , Animales , Ratones , Factor 2 Asociado a Receptor de TNF/metabolismo , Asma/metabolismo , Pulmón/metabolismo , Neutrófilos/metabolismo , Ubiquitinas/metabolismo , Inflamación/patologíaRESUMEN
Liver cancer is the sixth most common cancer and the third leading cause of cancer-related death globally. Despite efforts being made in last two decades in cancer diagnosis and treatment, the 5-year survival rate of liver cancer remains extremely low. TRIM21 participates in cancer metabolism, glycolysis, immunity, chemosensitivity and metastasis by targeting various substrates for ubiquitination. TRIM21 serves as a prognosis marker for human hepatocellular carcinoma (HCC), but the mechanism by which TRIM21 regulates HCC tumorigenesis and progression remains elusive. In this study, we demonstrated that TRIM21 protein levels were elevated in human HCC. Elevated TRIM21 expression was associated with HCC progression and poor survival. Knockdown of TRIM21 in HCC cell lines significantly impaired cell growth and metastasis and enhanced sorafenib-induced toxicity. Mechanistically, we found that knockdown of TRIM21 resulted in cytosolic translocation and inactivation of YAP. At the molecular level, we further identified that TRIM21 interacted and induced ubiquitination of MST1, which resulted in MST1 degradation and YAP activation. Knockdown of MST1 or overexpression of YAP reversed TRIM21 knockdown-induced impairment of HCC growth and chemosensitivity. Taken together, the current study demonstrates a novel mechanism that regulates the Hippo pathway and reveals TRM21 as a critical factor that promotes growth and chemoresistance in human HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ribonucleoproteínas , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Sorafenib/farmacología , Sorafenib/uso terapéutico , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Ubiquitinación , Proteínas Señalizadoras YAP/metabolismo , Proteínas Señalizadoras YAP/genéticaRESUMEN
Kirsten rat sarcoma virus protein (KRAS) is a protein that plays a central role in signal transduction using extracellular signal regulated kinase (ERK) and mitogen activated protein kinase (MAPK) cellular signaling pathway. KRAS is a frequently mutated oncogene and plays a pivotal role in tumor initiation and progression. Hotspot mutations on codon 12, 13 and 61 in KRAS are well-known for their role in drug resistance and non-hotspot mutations also play a significant part in contributing to resistance mechanisms. The understanding of how these non-hotspot mutations might affect the signal transduction of KRAS and their contribution towards drug resistance is understudied. Here we provide structural insights into the interaction of non-hotspot KRAS mutants with GTP (the native ligand) using a molecular docking and molecular dynamics simulation approach. Extensive molecular docking and simulation studies suggest that non-hotspot mutations (E31D and E63K) show stable interaction with native ligand using all five trajectories, as evidenced by root mean square of distance (RMSD), root mean square of fluctuation (RMSF), radius of gyration (RoG), coulomb short-range energy and MMGBSA analysis. These results suggest that non-hotspot mutations do not undermine the oncogenic nature of KRAS. This observation is consistent with previous findings where overexpressing E31D and E63K mutations share phenotypic features with G12D and G13D transfected cells, including increased proliferative capacity, actin cytoskeleton organization, and migration rates. We further test whether FDA-approved KRAS inhibitors sotorasib and adagrasib successfully inhibit the E31D and E63K mutants. Results suggest that these two non-hotspot mutants can be inhibited by both drugs with following trend of structural stability (E31D > E63K > wild-KRAS > Q61H > G12C). Based on sharp coherence in trajectories between wild KRAS and non-hotspot mutants, it is suggested that these novel mutants do not contribute to drug resistance mechanism. Overall, we provide a comprehensive understanding of the impact of non-hotspot mutations on KRAS and their potential as targets for effective cancer therapies.Communicated by Ramaswamy H. Sarma.
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Background: The purpose of this study was to critically review the existing literature on the effects of active video games (AVGs) on physical activity in overweight and obese college students to determine whether AVGs can promote and achieve recommended levels of physical activity. The results should provide constructive input for future research. Methods: A total of five international databases including PubMed, SCOPUS, Web of Science, CINAHL Plus, and EBSCOhost were searched with keywords related to "active video games," "physical activity," and "obese college students" from July 2022. A systematic review was conducted using the PRISMA guidelines and randomised controlled trial (RCT) studies that met the inclusion criteria were included. Furthermore, the quality assessment of the studies was measured using the PEDro scale. Results: One thousand and twenty-three articles were retrieved, of which eight randomised controlled trial studies met the inclusion criteria. AVGs can reduce sedentary behaviour and positively affect physical activity, time spent on moderate-to-vigorous physical activity (MVPA), positive psychological factors, and game attendance rate. Combining AVGs with other assistive devices (such as mini-trampolines and stationary bikes) can enhance the effects of AVGs and provide greater physiological stimulation. Different types of AVGs and game modes can achieve different emotional responses, physiological stimulation, and physical activity levels. Conclusion: The research findings prove that AVGs can be a viable intervention to increase physical activity in overweight or obese college students, ultimately reaching the recommended physical activity level(PAL). Physical activity can be further increased by incorporating assistive devices or using features supported by self-determination theory (SDT). As a new modality, AVGs could be a potential alternative to traditional physical activity.Systematic Review Registration:https://www.crd.york.ac.uk/prospero, identifier: CRD42022363993.
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Ejercicio Físico , Obesidad , Sobrepeso , Estudiantes , Juegos de Video , Humanos , Ejercicio Físico/psicología , Estudiantes/psicología , Universidades , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto Joven , MasculinoRESUMEN
The deleterious effects of mental fatigue (MF) on athletes have been carefully studied in various sports, such as soccer, badminton, and swimming. Even though many researchers have sought ways to ameliorate the negative impact of MF, there is still a lack of studies that review the interventions used to counteract MF among athletes. This review aims to report the current evidence exploring the effects of interventions on MF and sport-specific performance, including sport-specific motor performance and perceptual-cognitive skills. Web of Science, Scopus, PubMed, and SPORTDicus (EBSCOhost) were combed through to find relevant publications. Additionally, the references and Google Scholar were searched for any grey literature. For the current review, we included only randomized controlled trials that involved athletes, a primary task to induce MF, interventions to counter MF with comparable protocols, and the outcomes of sport-specific motor performance and perceptual-cognitive skill. The selection criteria resulted in the inclusion of 10 articles. The manipulations of autonomous self-control exertion, person-fit, nature exposure, mindfulness, and transactional direct current stimulation showed that positive interventions counteract MF and improve sport-specific performance in different domains, including strength, speed, skill, stamina, and perceptual-cognitive skills. The selected interventions could significantly counteract MF and improve subsequent sport-specific performance. Moreover, self-regulation and attention resources showed the importance of the potential mechanisms behind the relevant interventions.
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Atletas , Rendimiento Atlético , Fatiga Mental , Humanos , Fatiga Mental/prevención & control , Fatiga Mental/psicología , Rendimiento Atlético/psicología , Rendimiento Atlético/fisiología , Atletas/psicología , Atención Plena/métodosRESUMEN
OBJECTIVES: We aimed to develop a multi-modality model to predict axillary lymph node (ALN) metastasis by combining clinical predictors with radiomic features from magnetic resonance imaging (MRI) and mammography (MMG) in breast cancer. This model might potentially eliminate unnecessary axillary surgery in cases without ALN metastasis, thereby minimizing surgery-related complications. METHODS: We retrospectively enrolled 485 breast cancer patients from two hospitals and extracted radiomics features from tumor and lymph node regions on MRI and MMG images. After feature selection, three random forest models were built using the retained features, respectively. Significant clinical factors were integrated with these radiomics models to construct a multi-modality model. The multi-modality model was compared to radiologists' diagnoses on axillary ultrasound and MRI. It was also used to assist radiologists in making a secondary diagnosis on MRI. RESULTS: The multi-modality model showed superior performance with AUCs of 0.964 in the training cohort, 0.916 in the internal validation cohort, and 0.892 in the external validation cohort. It surpassed single-modality models and radiologists' ALN diagnosis on MRI and axillary ultrasound in all validation cohorts. Additionally, the multi-modality model improved radiologists' MRI-based ALN diagnostic ability, increasing the average accuracy from 70.70 to 78.16% for radiologist A and from 75.42 to 81.38% for radiologist B. CONCLUSION: The multi-modality model can predict ALN metastasis of breast cancer accurately. Moreover, the artificial intelligence (AI) model also assisted the radiologists to improve their diagnostic ability on MRI. CLINICAL RELEVANCE STATEMENT: The multi-modality model based on both MRI and mammography images allows preoperative prediction of axillary lymph node metastasis in breast cancer patients. With the assistance of the model, the diagnostic efficacy of radiologists can be further improved. KEY POINTS: ⢠We developed a novel multi-modality model that combines MRI and mammography radiomics with clinical factors to accurately predict axillary lymph node (ALN) metastasis, which has not been previously reported. ⢠Our multi-modality model outperformed both the radiologists' ALN diagnosis based on MRI and axillary ultrasound, as well as single-modality radiomics models based on MRI or mammography. ⢠The multi-modality model can serve as a potential decision support tool to improve the radiologists' ALN diagnosis on MRI.
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As urban economies flourish and populations become increasingly concentrated, urban surface deformation has emerged as a critical factor in city planning that cannot be overlooked. Surface deformation in urban areas can lead to deformations in structural supports of infrastructure such as road bases and bridges, thereby posing a serious threat to public safety and creating significant safety hazards. Consequently, research focusing on the monitoring of urban surface deformation holds paramount importance. Interferometric synthetic aperture radar (InSAR), as an important means of earth observation, has all-day, wide-range, high-precision, etc., characteristics and is widely used in the field of surface deformation monitoring. However, traditional solitary InSAR techniques are limited in their application scenarios and computational characteristics. Additionally, the manual selection of ground control points (GCPs) is fraught with errors and uncertainties. Permanent scatterers (PS) can maintain high interferometric coherence in man-made building areas, and distributed scatterers (DS) usually show moderate coherence in areas with short vegetation; the combination of DS and PS solves the problem of manually selecting GCPs during track re-flattening and regrading, which affects the monitoring results. In this paper, 45 Sentinel-1B data from 16 February 2019 to 14 December 2021 are used as the data source in the urban area of Horqin District, Tongliao City, Inner Mongolia Autonomous Region, for example. A four-threshold (coherence coefficient threshold, FaSHPS adaptive threshold, amplitude divergence index threshold, and deformation velocity interval) GCPs point screening method for PS-DS, as well as a Small Baseline Subset-Permanent Scatterers-Distributed Scatterers-Interferometric Synthetic Aperture Radar (SBAS-PS-DS-InSAR) method for selecting PS and DS points as ground control points for orbit refinement and re-flattening, are proposed. The surface deformation results obtained using the Small Baseline Subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) and the SBAS-PS-DS-InSAR proposed in this paper were comparatively analysed and verified. The maximum cumulative line-of-sight settlements were -90.78 mm and -83.68 mm, and the maximum cumulative uplifts are 74.94 mm and 97.56 mm, respectively; the maximum annual average line-of-sight settlements are -35.38 mm/y and -30.38 mm/y, and the maximum annual average uplifts are 25.27 mm/y and 27.92 mm/y. The results were evaluated and analysed in terms of correlation, mean absolute error (MAE), and root mean square error (RMSE). The deformation results of the two InSAR methods were evaluated and analysed in terms of correlation, MAE, and RMSE. The errors show that the Pearson correlation coefficients between the vertical settlement results obtained using the SBAS-PS-DS-InSAR method and the GPS monitoring results were closer to 1. The maximum MAE and RMSE were 13.7625 mm and 14.8004 mm, respectively, which are within the acceptable range; this confirms that the monitoring results of the SBAS-PS-DS-InSAR method were better than those of the original SBAS-InSAR method. SBAS-InSAR method, which is valid and reliable. The results show that the surface deformation results obtained using the SBAS-InSAR, SBAS-PS-DS-InSAR, and GPS methods have basically the same settlement locations, extents, distributions, and temporal and spatial settlement patterns. The deformation results obtained using these two InSAR methods correlate well with the GPS monitoring results, and the MAE and RMSE are within acceptable limits. By comparing the deformation information obtained using multiple methods, the surface deformation in urban areas can be better monitored and analysed, and it can also provide scientific references for urban municipal planning and disaster warning.
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The protein 4.1R is an essential component of the erythrocyte membrane skeleton, serving as a key structural element and contributing to the regulation of the membrane's physical properties, including mechanical stability and deformability, through its interaction with spectrin-actin. Recent research has uncovered additional roles of 4.1R beyond its function as a linker between the plasma membrane and the membrane skeleton. It has been found to play a crucial role in various biological processes, such as cell fate determination, cell cycle regulation, cell proliferation, and cell motility. Additionally, 4.1R has been implicated in cancer, with numerous studies demonstrating its potential as a diagnostic and prognostic biomarker for tumors. In this review, we provide an updated overview of the gene and protein structure of 4.1R, as well as its cellular functions in both physiological and pathological contexts.
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Proteínas del Citoesqueleto , Proteínas de la Membrana , Proteínas de la Membrana/metabolismo , Proteínas del Citoesqueleto/metabolismo , Espectrina/química , Espectrina/genética , Espectrina/metabolismo , Actinas/metabolismo , Membrana Eritrocítica/metabolismoRESUMEN
Abnormal activation of the oncogene YAP in the Hippo pathway is a major feature in liver cancer and inactivation of MST1/2 has been shown to be responsible for the overactivation of YAP that led to tumorigenesis. However, mechanisms underlying MST1/2 dysregulation remain poorly understood. RNA-seq analysis and genome (KEGG) pathway enrichment analysis were used to identify genes and pathways that were regulated by SIRT7. qRT-PCR, ChIP, and luciferase assay were used to investigate transcriptional regulation. Mass spectrometry, co-immunoprecipitation and immunoprecipitation were used to exam protein-protein interaction and post-transcriptional modification. A xenograft mouse model was used to confirm the effect of SIRT7 and SIRT7 inhibitors on hepatocellular carcinoma (HCC) proliferation in vivo. We found that SIRT7 suppresses MST1 by both transcriptional regulation and post-transcriptional modification, which in turn promotes YAP nuclear localization and transcriptional activation in liver cancer. Mechanistically, we revealed that SIRT7 suppresses MST1 transcription by binding to the MST1 promoter and inducing H3K18 deacetylation in its promoter region. In addition, SIRT7 directly binds to and deacetylates MST1, which primes acetylation-dependent MST1 ubiquitination and protein degradation. In clinical samples, we confirmed a negative correlation between SIRT7 and MST1 protein levels, and high SIRT7 expression correlated with elevated YAP expression and nuclear localization. In addition, SIRT7 specific inhibitor 2800Z sufficiently inhibited HCC growth by disrupting the SIRT7/MST1/YAP axis. Our data thus revealed the previously undescribed function of SIRT7 in regulating the Hippo pathway in HCC and further proved that targeting SIRT7 might provide novel therapeutic options for the treatment of liver cancer.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sirtuinas , Humanos , Ratones , Animales , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Transducción de Señal , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proliferación Celular/genética , Sirtuinas/genética , Sirtuinas/metabolismoRESUMEN
BACKGROUND AND AIM: Hepatotoxicity is a well-defined reaction to methotrexate (MTX), a drug commonly used for the treatment of rheumatoid arthritis and various tumours. We sought to elucidate the mechanism underlying MTX-induced hepatotoxicity and establish a potentially effective intervention strategy. METHODS: We administered MTX to liver cells and mice and assessed hepatotoxicity by cell viability assay and hepatic pathological changes. We determined ferroptosis and ferritinophagy by detecting ferroptosis-related markers and autophagic degradation of ferritin heavy chain 1 (FTH1). RESULTS: We have shown that hepatocytes treated with MTX undergo ferroptosis, and this process can be attenuated by ferroptosis inhibitors. Interestingly, NCOA4-mediated ferritinophagy was found to be involved in MTX-induced ferroptosis, which was demonstrated by the relief of ferroptosis through the inhibition of autophagy or knockdown of Ncoa4. Furthermore, MTX treatment resulted in the elevation of high-mobility group box 1 (HMGB1) expression. The depletion of Hmgb1 in hepatocytes considerably alleviated MTX-induced hepatotoxicity by limiting autophagy and the subsequent autophagy-dependent ferroptosis. It is noteworthy that glycyrrhizic acid (GA), a precise inhibitor of HMGB1, effectively suppressed autophagy, ferroptosis and hepatotoxicity caused by MTX. CONCLUSION: Our study shows the significant roles of autophagy-dependent ferroptosis and HMGB1 in MTX-induced hepatotoxicity. It emphasizes that the inhibition of ferritinophagy and HMGB1 may have potential as a therapeutic approach for preventing and treating MTX-induced liver injury.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Ferroptosis , Proteína HMGB1 , Animales , Ratones , Autofagia , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Metotrexato/toxicidad , Metotrexato/uso terapéuticoRESUMEN
BACKGROUND: The preoperative diagnosis of peritoneal metastasis (PM) in epithelial ovarian cancer (EOC) is challenging and can impact clinical decision-making. PURPOSE: To investigate the performance of T2 -weighted (T2W) MRI-based deep learning (DL) and radiomics methods for PM evaluation in EOC patients. STUDY TYPE: Retrospective. POPULATION: Four hundred seventy-nine patients from five centers, including one training set (N = 297 [mean, 54.87 years]), one internal validation set (N = 75 [mean, 56.67 years]), and two external validation sets (N = 53 [mean, 55.58 years] and N = 54 [mean, 58.22 years]). FIELD STRENGTH/SEQUENCE: 1.5 or 3 T/fat-suppression T2W fast or turbo spin-echo sequence. ASSESSMENT: ResNet-50 was used as the architecture of DL. The largest orthogonal slices of the tumor area, radiomics features, and clinical characteristics were used to construct the DL, radiomics, and clinical models, respectively. The three models were combined using decision-level fusion to create an ensemble model. Diagnostic performances of radiologists and radiology residents with and without model assistance were evaluated. STATISTICAL TESTS: Receiver operating characteristic analysis was used to assess the performances of models. The McNemar test was used to compare sensitivity and specificity. A two-tailed P < 0.05 was considered significant. RESULTS: The ensemble model had the best AUCs, outperforming the DL model (0.844 vs. 0.743, internal validation set; 0.859 vs. 0.737, external validation set I) and clinical model (0.872 vs. 0.730, external validation set II). After model assistance, all readers had significantly improved sensitivity, especially for those with less experience (junior radiologist1, from 0.639 to 0.820; junior radiologist2, from 0.689 to 0.803; resident1, from 0.623 to 0.803; resident2, from 0.541 to 0.738). One resident also had significantly improved specificity (from 0.633 to 0.789). DATA CONCLUSIONS: T2W MRI-based DL and radiomics approaches have the potential to preoperatively predict PM in EOC patients and assist in clinical decision-making. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.