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The Wacker and Wacker-type reactions are some of the most fundamental and powerful transformations in organic chemistry for their ability to efficiently produce valuable chemicals. Remarkable progress has been achieved in asymmetric oxy/aza-Wacker-type reactions; however, asymmetric Wacker-type dicarbofunctionalization remains underdeveloped, especially for the concurrent construction of two stereocenters. Herein, we report a Pd/Cu-cocatalyzed enantio- and diastereodivergent Wacker-type dicarbofunctionalization of alkene-tethered aryl triflates with imino esters. A series of 2-indanyl motifs bearing adjacent carbon stereocenters could be easily synthesized in moderate to excellent yields and with good to excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). Density functional theory calculations revealed that the origin of diastereoselectivity in this Pd/Cu synergistic catalytic system is jointly determined by both the intermolecular anti-carbopalladation of alkenes and the reductive elimination processes, in accordance with the Curtin-Hammett principle.
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Edema of the prepuce is a common clinical complication following circumcision in urology. Nevertheless, the principal method of gauze wrapping in clinical practice has not yet been demonstrated to be an effective solution to the problem of postoperative edema. It is therefore evident that the development of functional dressings for the treatment of post-circumcision edema has considerable potential for both clinical application and translational significance. The objective of this study was to develop a single-component bioactive oligopeptide hydrogel dressing with favorable anti-inflammatory, pro-angiogenesis properties and biosafety for the treatment of edema following prepuce surgery. A hexapeptide (Ac-FFFGHK-OH) hydrogelator was designed and synthesized through the N-terminal modification of a human-derived glycine-histidine-lysine tripeptide (GHK) with an N-acetylated phenylalanine tripeptide (Ac-FFF). The bioactive Ac-FFFGHK-OH hydrogel can be prepared through a facile self-assembly method. Furthermore, a novel experimental animal model of post-circumcision edema in Sprague-Dawley rats was constructed and the in vivo anti-edema effect of the Ac-FFFGHK-OH hydrogel was confirmed. The mechanism of action in relieving edema was also investigated by in vitro cell experiments. This work may inspire alternative thinking for the development of mono-component bioactive oligopeptide hydrogels for the treatment of edema in various diseases.
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Endothelial dysfunction contributes to the pathogenesis of Takotsubo syndrome (TTS). However, the exact mechanism underlying endothelial dysfunction in the setting of TTS has not been completely clarified. This study aims to investigate the roles of angiotensin II (Ang II) and intermediate-conductance Ca2+-activated K+ (SK4) channels in catecholamine-induced endothelial dysfunction. Human cardiac microvascular endothelial cells (HCMECs) were exposed to 100⯵M epinephrine (Epi), mimicking the setting of TTS. Epi treatment increased the ET-1 concentration and reduced NO levels in HCMECs. Importantly, the effects of Epi were found to be mitigated in the presence of Ang II receptor blockers. Furthermore, Ang II mimicked Epi effects on ET-1 and NO production. Additionally, Ang II inhibited tube formation and increased cell apoptosis. The effects of Ang II could be reversed by an SK4 activator NS309 and mimicked by an SK4 channel blocker TRAM-34. Ang II also inhibited the SK4 channel current (ISK4) without affecting its expression level. Ang II could depolarize the cell membrane potential. Ang II promoted ROS release and reduced protein kinase A (PKA) expression. A ROS blocker prevented Ang II effect on ISK4. The PKA activator Sp-8-Br-cAMPS increased SK4 channel currents. Epinephrine enhanced the activity of ACE by activating the α1 receptor/Gq/PKC signal pathway, thereby promoting the secretion of Ang II. The study suggested that high-level catecholamine can increase Ang II release from endothelial cells by α1 receptors/Gq/PKC signal pathway. Ang II can inhibit SK4 channel current by increasing ROS generation and reducing PKA expression, thereby contributing to endothelial dysfunction.
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Angiotensina II , Catecolaminas , Células Endoteliales , Especies Reactivas de Oxígeno , Angiotensina II/farmacología , Humanos , Catecolaminas/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Epinefrina/farmacología , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Apoptosis/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Óxido Nítrico/metabolismo , Transducción de Señal/efectos de los fármacos , Células CultivadasRESUMEN
PURPOSE: To investigate the performance of histogram features of non-Gaussian diffusion metrics for diagnosing muscle invasion and histological grade in bladder cancer (BCa). METHODS: Patients were prospectively allocated to MR scanner1 (training cohort) or MR2 (testing cohort) for conventional diffusion-weighted imaging (DWIconv) and multi-b-value DWI. Metrics of continuous time random walk (CTRW), diffusion kurtosis imaging (DKI), fractional-order calculus (FROC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) were simultaneously calculated using multi-b-value DWI. Whole-tumor histogram features were extracted from DWIconv and non-Gaussian diffusion metrics for logistic regression analysis to develop diffusion models diagnosing muscle invasion and histological grade. The models' performances were quantified by area under the receiver operating characteristic curve (AUC). RESULTS: MR1 included 267 pathologically-confirmed BCa patients (median age, 67 years [IQR, 46-82], 222 men) and MR2 included 83 (median age, 65 years [IQR, 31-82], 73 men). For discriminating muscle invasion, CTRW achieved the highest testing AUC of 0.915, higher than DWIconv's 0.805 (p = 0.014), and similar to the combined diffusion model's AUC of 0.885 (p = 0.076). For differentiating histological grade of non-muscle-invasion bladder cancer, IVIM outperformed a testing AUC of 0.897, higher than DWIconv's 0.694 (p = 0.020), and similar to the combined diffusion model's AUC of 0.917 (p = 0.650). In both tasks, DKI, FROC, and SEM failed to show diagnostic superiority over DWIconv (p > 0.05). CONCLUSION: CTRW and IVIM are two potential non-Gaussian diffusion models to improve the MRI application in assessing muscle invasion and histological grade of BCa, respectively. CRITICAL RELEVANCE STATEMENT: Our study validates non-Gaussian diffusion imaging as a reliable, non-invasive technique for early assessment of muscle invasion and histological grade in BCa, enhancing accuracy in diagnosis and improving MRI application in BCa diagnostic procedures. KEY POINTS: Muscular invasion largely determines bladder salvageability in bladder cancer patients. Evaluated non-Gaussian diffusion metrics surpassed DWIconv in BCa muscle invasion and histological grade diagnosis. Non-Gaussian diffusion imaging improved MRI application in preoperative diagnosis of BCa.
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OBJECTIVE: High-risk types of diffuse gliomas in adults include isocitrate dehydrogenase (IDH) wild-type glioblastomas and grade 4 astrocytomas. Achieving noninvasive prediction of high-risk molecular subtypes of gliomas is important for personalized and precise diagnosis and treatment. METHODS: We retrospectively collected data from 116 patients diagnosed with adult diffuse gliomas. Multiple high-risk molecular markers were tested, and various habitat models and whole-tumor models were constructed based on preoperative routine and diffusion kurtosis imaging (DKI) sequences to predict high-risk molecular subtypes of gliomas. Feature selection and model construction utilized Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Finally, the Wilcoxon rank-sum test was employed to explore the correlation between habitat quantitative features (intra-tumor heterogeneity scoreï¼ITH score) and heterogeneity, as well as high-risk molecular subtypes. RESULTS: The results showed that the habitat analysis model based on DKI performed remarkably well (with AUC values reaching 0.977 and 0.902 in the training and test sets, respectively). The model's performance was further enhanced when combined with clinical variables. (The AUC values were 0.994 and 0.920, respectively.) Additionally, we found a close correlation between ITH score and heterogeneity, with statistically significant differences observed between high-risk and non-high-risk molecular subtypes. INTERPRETATION: The habitat model based on DKI is an ideal means for preoperatively predicting high-risk molecular subtypes of gliomas, holding significant value for noninvasively alerting malignant gliomas and those with malignant transformation potential.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Femenino , Masculino , Persona de Mediana Edad , Glioma/diagnóstico por imagen , Glioma/genética , Adulto , Estudios Retrospectivos , Anciano , Imagen de Difusión Tensora/métodos , Adulto JovenRESUMEN
BACKGROUND: Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time. METHODS: This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator . Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves. RESULTS: In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63-0.96) and 0.77(95%CI:0.60-0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55-0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model. CONCLUSION: The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance.
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Imagenología Tridimensional , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Masculino , Femenino , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico por imagen , Estudios Prospectivos , Imagenología Tridimensional/métodos , Anciano , Imagen por Resonancia Magnética/métodos , Curva ROC , Nomogramas , RadiómicaRESUMEN
Optimizing the antibacterial effectiveness of copper ions while reducing environmental and cellular toxicity is essential for public health. A copper chelate, named PAI-Cu, is skillfully created using a specially designed carboxyl copolymer (a combination of acrylic and itaconic acids) with copper ions. PAI-Cu demonstrates a broad-spectrum antibacterial capability both in vitro and in vivo, without causing obvious cytotoxic effects. When compared to free copper ions, PAI-Cu displays markedly enhanced antibacterial potency, being about 35 times more effective against Escherichia coli and 16 times more effective against Staphylococcus aureus. Moreover, Gaussian and ab initio molecular dynamics (AIMD) analyses reveal that Cu+ ions can remain stable in the carboxyl compound's aqueous environment. Thus, the superior antibacterial performance of PAI-Cu largely stems from its modulation of copper ions between mono- and divalent states within the Cu-carboxyl chelates, especially via the carboxyl ligand. This modulation leads to the generation of reactive oxygen species (ËOH), which is pivotal in bacterial eradication. This research offers a cost-effective strategy for amplifying the antibacterial properties of Cu ions, paving new paths for utilizing copper ions in advanced antibacterial applications.
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Antibacterianos , Quelantes , Cobre , Escherichia coli , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Cobre/química , Cobre/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Escherichia coli/efectos de los fármacos , Quelantes/química , Quelantes/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Ratones , Especies Reactivas de Oxígeno/metabolismo , Estructura MolecularRESUMEN
A hydrogen-bonded organic framework (HOF) consisting of a 9,10-diphenylanthracene carboxylic derivative, DPACOOH, was developed for solid state triplet-triplet annihilation upconversion (TTA-UC). The HOF sample shows a 70% increase in upconversion quantum yield and a lower threshold value of 126.0 mW cm-2 compared to those of the disordered powder sample, due to a 43% longer triplet diffusion length in HOF than that in the powder sample.
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To break the resolution limitation of traditional resists, more work is needed on non-chemically amplified resists (non-CARs). Non-CARs based on iodonium salt modified polystyrene (PS-I) were prepared with controllable molecular weight and structure. The properties of the resist can be adjusted by the uploading of iodonium salts on the polymer chain, the materials with a higher proportion of iodonium salts show better lithography performance. By comparing contrast curves and quality of the lithographic patterns, the optimum developing condition of 4-methyl-2-pentanone and ethyl alcohol (v:v = 1:7) was selected. The high-resolution stripes of 15 nm half-pitch (HP) can be achieved by PS-I0.58in e-beam lithography (EBL). PS-I0.58shows the advanced lithography performance in the patterns of 16 nm HP and 18 nm HP stripes with low line edge roughness (3.0 nm and 2.4 nm). The resist shows excellent potential for further pattern transfer, the etch selectivity of resist PS-I0.58to the silicon was close to 12:1. The lithographic mechanism of PS-I was investigated by experimental and theoretical calculation, which indicates the polarity of materials changes results in the solubility switch. This work provides a new option and useful guidelines for the development of high-resolution resist.
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Background: Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH. Notably, the iron-quercetin complex (IronQ), a metal-quercetin complex synthesized through coordination chemistry, has garnered significant attention for its biomedical applications. In our previous studies, we have observed that IronQ exerts stimulatory effects on cell growth, notably enhancing the survival and viability of peripheral blood mononuclear cells (PBMCs) and MSCs. This study aimed to evaluate the effects of pretreated MSCs with IronQ on neuroinflammation and elucidate its underlying mechanisms. Methods: The ICH mice were induced by injecting the collagenase I solution into the right brain caudate nucleus. After 24 hours, the ICH mice were randomly divided into four subgroups, the model group (Model), quercetin group (Quercetin), MSCs group (MSCs), and pretreated MSCs with IronQ group (MSCs+IronQ). Neurological deficits were re-evaluated on day 3, and brain samples were collected for further analysis. TUNEL staining was performed to assess cell DNA damage, and the protein expression levels of inflammatory factors and the cGAS-STING signaling pathway were investigated and analyzed. Results: Pretreated MSCs with IronQ effectively mitigate neurological deficits and reduce neuronal inflammation by modulating the microglial polarization. Moreover, the pretreated MSCs with IronQ suppress the protein expression levels of the cGAS-STING signaling pathway. Conclusion: These findings suggest that pretreated MSCs with IronQ demonstrate a synergistic effect in alleviating neuroinflammation, thereby improving neurological function, which is achieved through the inhibition of the cGAS-STING signaling pathway.
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OBJECTIVE: We aimed to develop a radiomics-clinical nomogram using multi-sequence MRI to predict recurrence-free survival (RFS) in bladder cancer (BCa) patients and assess its superiority over clinical models. METHODS: A retrospective cohort of 229 BCa patients with preoperative multi-sequence MRI was divided into a training set (n = 160) and a validation set (n = 69). Radiomics features were extracted from T2-weighted images, diffusion-weighted imaging, apparent diffusion coefficient, and dynamic contrast-enhanced images. Effective features were identified using the least absolute shrinkage and selection operator (LASSO) method. Clinical risk factors were determined via univariate and multivariate Cox analysis, leading to the creation of a radiomics-clinical nomogram. Kaplan-Meier analysis and log-rank tests assessed the relationship between radiomics features and RFS. We calculated the net reclassification improvement (NRI) to evaluate the added value of the radiomics signature and used decision curve analysis (DCA) to assess the nomogram's clinical validity. RESULTS: Radiomics features significantly correlated with RFS (log-rank p < 0.001) and were independent of clinical factors (p < 0.001). The combined model, incorporating radiomics features and clinical data, demonstrated the best prognostic value, with C-index values of 0.853 in the training set and 0.832 in the validation set. Compared to the clinical model, the radiomics-clinical nomogram exhibited superior calibration and classification (NRI: 0.6768, 95% CI: 0.5549-0.7987, p < 0.001). CONCLUSION: The radiomics-clinical nomogram, based on multi-sequence MRI, effectively assesses the BCa recurrence risk. It outperforms both the radiomics model and the clinical model in predicting BCa recurrence risk. CRITICAL RELEVANCE STATEMENT: The radiomics-clinical nomogram, utilizing multi-sequence MRI, holds promise for predicting bladder cancer recurrence, enhancing individualized clinical treatment, and performing tumor surveillance. KEY POINTS: ⢠Radiomics plays a vital role in predicting bladder cancer recurrence. ⢠Precise prediction of tumor recurrence risk is crucial for clinical management. ⢠MRI-based radiomics models excel in predicting bladder cancer recurrence.
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The emergence of acute ischemic stroke (AIS) induced cardiovascular dysfunctions as a bidirectional interaction has gained paramount importance in understanding the intricate relationship between the brain and heart. Post AIS, the ensuing cardiovascular dysfunctions encompass a spectrum of complications, including heart attack, congestive heart failure, systolic or diastolic dysfunction, arrhythmias, electrocardiographic anomalies, hemodynamic instability, cardiac arrest, among others, all of which are correlated with adverse outcomes and mortality. Mounting evidence underscores the intimate crosstalk between the heart and the brain, facilitated by intricate physiological and neurohumoral complex networks. The primary pathophysiological mechanisms contributing to these severe cardiac complications involve the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic and parasympathetic hyperactivity, immune and inflammatory responses, and gut dysbiosis, collectively shaping the stroke-related brain-heart axis. Ongoing research endeavors are concentrated on devising strategies to prevent AIS-induced cardiovascular dysfunctions. Notably, labetalol, nicardipine, and nitroprusside are recommended for hypertension control, while ß-blockers are employed to avert chronic remodeling and address arrhythmias. However, despite these therapeutic interventions, therapeutic targets remain elusive, necessitating further investigations into this complex challenge. This review aims to delineate the state-of-the-art pathophysiological mechanisms in AIS through preclinical and clinical research, unraveling their intricate interplay within the brain-heart axis, and offering pragmatic suggestions for managing AIS-induced cardiovascular dysfunctions.
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Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Corazón , Accidente Cerebrovascular/complicaciones , EncéfaloRESUMEN
Fluorescent mechanophores can indicate the deformation or damage in polymers. The development of mechanophores with multi-triggered response is of great interest. Herein, Diels-Alder (DA) adducts are incorporated into linear poly(methyl acrylate) PMA-BA and network poly(hexyl methacrylate) (PHMA) as mechanophores to detect the stress caused by ultrasound, freezing, and compression. The DA mechanophores undergo retro-DA reaction to release 9-styrylanthracene chromophore upon applying force, resulting in cyan fluorescence. The dissociation ratio of the DA mechanophore after pulsed ultrasonication of PMA-BA solution for 240 minutes is estimated to be 52 % by absorption spectra and 1H NMR. Additionally, the rate constant of mechanical cleavage is calculated to be 1.2×10-4â min-1â kDa-1 with the decrease in molecular weight from 69 to 22â kDa measured by gel permeation chromatography. Freezing of PHMA gels as well as compression of PHMA bulk samples turn-on the DA mechanophores, revealing the microscale fracture. Photon upconversion responses toward various force stimuli are also achieved in both polymer solutions and bulk samples by doping platinum octaethylporphyrin (PtOEP) or palladium meso-tetraphenyltetrabenzoporphyrin (PdTPTBP) sensitizers with multiple excitation wavelengths.
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ß-Galactosidase (ß-gal), which is responsible for the hydrolysis of the glycosidic bond of lactose to galactose, has been recognized as an important biomarker of cell or organism status, especially cell senescence and primary ovarian cancer. Extensive efforts have been devoted to develop probes for detecting and visualizing ß-gal in cells. Herein, a fluorescent probe gal-HCA which possesses both excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) properties was prepared to monitor ß-gal in living cells. The probe consists of 2-hydroxy-4'-dimethylamino-chalcone (HCA) capped with a D-galactose group. The cleavage of the glycosidic bond in gal-HCA triggered by ß-gal releases HCA, which results in a significant bathochromic shift in fluorescence from 532 to 615 nm. The probe exhibited high selectivity and sensitivity toward ß-gal with a detection limit as low as 0.0122 U mL-1. The confocal imaging investigation demonstrated the potential of gal-HCA in monitoring the endocellular overexpressed ß-gal in senescent cells and ovarian cancer cells. This study provides a straightforward approach for the development of fluorescent probes to monitor ß-gal and detection of ß-gal-associated diseases.
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Chalconas , Neoplasias Ováricas , Femenino , Humanos , Colorantes Fluorescentes/química , Protones , Neoplasias Ováricas/diagnóstico por imagen , Imagen Óptica/métodos , beta-GalactosidasaRESUMEN
This study aimed to investigate the relationship between exercise addiction and brain structure in middle-older individuals, and to examine the role of self-efficacy in mediating physiological changes associated with exercise addiction. A total of 133 patients exhibiting symptoms of exercise addiction were recruited for this study (male = 43, age 52.86 ± 11.78 years). Structural magnetic resonance imaging and behavioral assessments were administered to assess the study population. Voxel-based morphological analysis was conducted using SPM12 software. Mediation analysis was employed to explore the potential neuropsychological mechanism of self-efficacy in relation to exercise addiction. The findings revealed a positive correlation between exercise addiction and gray matter volume in the right inferior temporal region and the right hippocampus. Conversely, there was a negative correlation with gray matter volume in the left Rolandic operculum. Self-efficacy was found to indirectly influence exercise addiction by affecting right inferior temporal region gray matter volume and acted as a mediating variable in the relationship between the gray matter volume of right inferior temporal region and exercise addiction. In summary, this study elucidates the link between exercise addiction and brain structure among middle-older individuals. It uncovers the intricate interplay among exercise addiction, brain structure, and psychological factors. These findings enhance our comprehension of exercise addiction and offer valuable insights for the development of interventions and treatments.
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Encéfalo , Autoeficacia , Humanos , Masculino , Adulto , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Lóbulo Parietal , Programas Informáticos , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVES: To develop an MRI radiomic nomogram capable of identifying muscle invasive bladder cancer (MIBC) patients with high-risk molecular characteristics related to poor 2-year disease-free survival (DFS). METHODS: We performed a retrospective analysis of DNA sequencing data, prognostic information, and radiomics features from 91 MIBC patients at stages T2-T4aN0M0 without history of immunotherapy. To identify risk stratification, we employed Cox regression based on TP53 mutation status and tumor mutational burden (TMB) level. Radiomics signatures were selected using the least absolute shrinkage and selection operator (LASSO) to construct a nomogram based on logistic regression for predicting the stratification in the training cohort. The predictive performance of the nomogram was assessed in the testing cohort using receiver operator curve (ROC), Hosmer-Lemeshow (HL) test, clinical impact curve (CIC), and decision curve analysis (DCA). RESULTS: Among 91 participants, the mean TMB value was 3.3 mut/Mb, with 60 participants having TP53 mutations. Patients with TP53 mutations and a below-average TMB value were identified as high risk and had a significantly poor 2-year DFS (hazard ratio = 4.36, 95% CI 1.82-10.44, P < 0.001). LASSO identified five radiomics signatures that correlated with the risk stratification. In the testing cohort, the nomogram achieved an area under the ROC curve of 0.909 (95% CI 0.789-0.991) and an accuracy of 0.889 (95% CI 0.708-0.977). CONCLUSION: The molecular risk stratification based on TP53 mutation status combined with TMB level is strongly associated with DFS in MIBC. Radiomics signatures can effectively predict this stratification and provide valuable information to clinical decision-making.
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Neoplasias , Radiómica , Humanos , Supervivencia sin Enfermedad , Estudios Retrospectivos , Imagen por Resonancia Magnética , MúsculosRESUMEN
The efficient detection and counting of pig populations is critical for the promotion of intelligent breeding. Traditional methods for pig detection and counting mainly rely on manual labor, which is either time-consuming and inefficient or lacks sufficient detection accuracy. To address these issues, a novel model for pig detection and counting based on YOLOv5 enhanced with shuffle attention (SA) and Focal-CIoU (FC) is proposed in this paper, which we call YOLOv5-SA-FC. The SA attention module in this model enables multi-channel information fusion with almost no additional parameters, enhancing the richness and robustness of feature extraction. Furthermore, the Focal-CIoU localization loss helps to reduce the impact of sample imbalance on the detection results, improving the overall performance of the model. From the experimental results, the proposed YOLOv5-SA-FC model achieved a mean average precision (mAP) and count accuracy of 93.8% and 95.6%, outperforming other methods in terms of pig detection and counting by 10.2% and 15.8%, respectively. These findings verify the effectiveness of the proposed YOLOv5-SA-FC model for pig population detection and counting in the context of intelligent pig breeding.
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Arrhythmogenic cardiomyopathy (ACM) is a hereditary myocardial disease characterized by the replacement of the ventricular myocardium with fibrous fatty deposits. ACM is usually inherited in an autosomal dominant pattern with variable penetrance and expressivity, which is mainly related to ventricular tachyarrhythmia and sudden cardiac death (SCD). Importantly, significant progress has been made in determining the genetic background of ACM due to the development of new techniques for genetic analysis. The exact molecular pathomechanism of ACM, however, is not completely clear and the genotype-phenotype correlations have not been fully elucidated, which are useful to predict the prognosis and treatment of ACM patients. Different gene-targeted and transgenic animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models, and heterologous expression systems have been developed. Here, this review aims to summarize preclinical ACM models and platforms promoting our understanding of the pathogenesis of ACM and assess their value in elucidating the ACM genotype-phenotype relationship.
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Ventrículos Cardíacos , Células Madre Pluripotentes Inducidas , Animales , Humanos , Miocardio , Miocitos CardíacosRESUMEN
2-Aminoanthracene was used as a nucleophilic additive in a molecular glass photoresist, bisphenol A derivative (BPA-6-epoxy), to improve advanced lithography performance. The effect of 2-aminoanthracene on BPA-6-epoxy was studied by electron beam lithography (EBL) and extreme ultraviolet lithography (EUVL). The result indicates that the additive can optimize the pattern outline by regulating epoxy cross-linking reaction, avoiding photoresist footing effectively in EBL. The EUVL result demonstrates that 2-aminoanthracene can significantly reduce line width roughness (LWR) for HP (Half-Pitch) 25 nm (from 4.9 to 3.8 nm) and HP 22 nm (from 6.9 to 3.0 nm). The power spectrum density (PSD) curve further confirms the reduction of roughness at medium and high frequency for HP 25 nm and the whole range of frequency for HP 22 nm, respectively. The study offers useful guidelines to improve the roughness of a chemically amplified molecular glass photoresist with epoxy groups for electron beam lithography and extreme ultraviolet lithography.