RESUMEN
Cognitive impairment is a common symptom of multiple sclerosis and profoundly impacts quality of life. Glutathione (GSH) and glutamate (Glu) are tightly linked in the brain, participating in cognitive function. However, GSH-Glu couplings in cognitive brain regions and their relationship with cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) remains unclear. Forty-one RRMS patients and 43 healthy controls underwent magnetic resonance spectroscopy to measure GSH and Glu levels in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus. Neuropsychological tests were used to evaluate the cognitive function. The Glu/GSH ratio was used to indicate the coupling between GSH and Glu and was tested as a predictor of cognitive performance. The results show that RRMS patients exhibited reduced hippocampal GSH and Glu levels, which were found to be significant predictors of worse verbal and visuospatial memory, respectively. Moreover, GSH levels were dissociated from Glu levels in the left hippocampus of RRMS patients. Hippocampal Glu/GSH ratio is significantly correlated with processing speed and has a greater predictive effect. Here we show the hippocampal Glu/GSH ratio could serve as a new potential marker for characterizing cognitive impairment in RRMS, providing a new direction for clinical detection of cognitive impairment.
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Disfunción Cognitiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/patología , Ácido Glutámico , Calidad de Vida , Imagen por Resonancia Magnética , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Pruebas NeuropsicológicasRESUMEN
Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated. Point RESolved Spectroscopy and Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy techniques were utilized to evaluate gamma-aminobutyric acid, glutamate, glutathione levels, and excitation/inhibition balance in the anterior cingulate cortex, posterior cingulate cortex, and occipital cortex of 39 neuromyelitis optica spectrum disorder patients and 41 healthy controls. Cognitive function was assessed using neurocognitive scales. Results showed decreased gamma-aminobutyric acid levels alongside increased glutamate, glutathione, and excitation/inhibition ratio in the anterior cingulate cortex and posterior cingulate cortex of neuromyelitis optica spectrum disorder patients. Specifically, within the posterior cingulate cortex of neuromyelitis optica spectrum disorder patients, decreased gamma-aminobutyric acid levels and increased excitation/inhibition ratio correlated significantly with anxiety scores, whereas glutathione levels predicted diminished executive function. The results suggest that neuromyelitis optica spectrum disorder patients exhibit dysregulation in the GABAergic and glutamatergic systems in their brains, where the excitation/inhibition imbalance potentially acts as a neuronal metabolic factor contributing to emotional disorders. Additionally, glutathione levels in the posterior cingulate cortex region may serve as predictors of cognitive decline, highlighting the potential benefits of reducing oxidative stress to safeguard cognitive function in neuromyelitis optica spectrum disorder patients.
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Ácido Glutámico , Giro del Cíngulo , Espectroscopía de Resonancia Magnética , Neuromielitis Óptica , Ácido gamma-Aminobutírico , Humanos , Giro del Cíngulo/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Femenino , Adulto , Neuromielitis Óptica/metabolismo , Neuromielitis Óptica/diagnóstico por imagen , Masculino , Ácido Glutámico/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Persona de Mediana Edad , Ácido gamma-Aminobutírico/metabolismo , Glutatión/metabolismo , Adulto Joven , Neurotransmisores/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/diagnóstico por imagenRESUMEN
Toll-interacting protein (Tollip) serves as a crucial inhibitory factor in the modulation of Toll-like receptor (TLR)-mediated innate immunological responses. The structure and function of Tollip have been well documented in mammals, yet the information in teleost remained limited. This work employed in vitro overexpression and RNA interference in vivo and in vitro to comprehensively examine the regulatory effects of AjTollip on NF-κB and MAPK signaling pathways. The levels of p65, c-Fos, c-Jun, IL-1, IL-6, and TNF-α were dramatically reduced following overexpression of AjTollip, whereas knocking down AjTollip in vivo and in vitro enhanced those genes' expression. Protein molecular docking simulations showed AjTollip interacts with AjTLR2, AjIRAK4a, and AjIRAK4b. A better understanding of the transcriptional regulation of AjTollip is crucial to elucidating the role of Tollip in fish antibacterial response. Herein, we cloned and characterized a 2.2 kb AjTollip gene promoter sequence. The transcription factors GATA1 and Sp1 were determined to be associated with the activation of AjTollip expression by using promoter truncation and targeted mutagenesis techniques. Collectively, our results indicate that AjTollip suppresses the NF-κB and MAPK signaling pathways, leading to the decreased expression of the downstream inflammatory factors, and GATA1 and Sp1 play a vital role in regulating AjTollip expression.
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Anguilla , Proteínas de Peces , Factor de Transcripción GATA1 , FN-kappa B , Animales , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/química , Proteínas de Peces/metabolismo , FN-kappa B/metabolismo , FN-kappa B/genética , Factor de Transcripción GATA1/genética , Factor de Transcripción GATA1/metabolismo , Anguilla/genética , Anguilla/inmunología , Factor de Transcripción Sp1/genética , Factor de Transcripción Sp1/metabolismo , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/inmunología , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/inmunología , Péptidos y Proteínas de Señalización Intracelular/química , Transducción de SeñalRESUMEN
Recent studies suggest that the interaction between presbycusis and cognitive impairment may be partially explained by the cognitive-ear link. However, the underlying neurophysiological mechanisms remain largely unknown. In this study, we combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) to investigate auditory gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, intra- and inter-network functional connectivity, and their relationships with auditory and cognitive function in 51 presbycusis patients and 51 well-matched healthy controls. Our results confirmed reorganization of the cognitive-ear link in presbycusis, including decreased auditory GABA and Glu levels and aberrant functional connectivity involving auditory networks (AN) and cognitive-related networks, which were associated with reduced speech perception or cognitive impairment. Moreover, mediation analyses revealed that decreased auditory GABA levels and dysconnectivity between the AN and default mode network (DMN) mediated the association between hearing loss and impaired information processing speed in presbycusis. These findings highlight the importance of AN-DMN dysconnectivity in cognitive-ear link reorganization leading to cognitive impairment, and hearing loss may drive reorganization via decreased auditory GABA levels. Modulation of GABA neurotransmission may lead to new treatment strategies for cognitive impairment in presbycusis patients.
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Disfunción Cognitiva , Presbiacusia , Humanos , Ácido Glutámico , Cognición , Ácido gamma-Aminobutírico , Disfunción Cognitiva/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
MAIN CONCLUSION: We review the application and the molecular regulation of anthocyanins in colorful Brassica crops, the creation of new germplasm resources, and the development and utilization of colorful Brassica crops. Brassica crops are widely cultivated: these include oilseed crops, such as rapeseed, mustards, and root, leaf, and stem vegetable types, such as turnips, cabbages, broccoli, and cauliflowers. Colorful variants exist of these crop species, and asides from increased aesthetic appeal, these may also offer advantages in terms of nutritional content and improved stress resistances. This review provides a comprehensive overview of pigmentation in Brassica as a reference for the selection and breeding of new colorful Brassica varieties for multiple end uses. We summarize the function and molecular regulation of anthocyanins in Brassica crops, the creation of new colorful germplasm resources via different breeding methods, and the development and multifunctional utilization of colorful Brassica crop types.
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Brassica napus , Brassica , Brassica/genética , Antocianinas , FitomejoramientoRESUMEN
BACKGROUND: Brain metastasis (BM) is a serious neurological complication of cancer of different origins. The value of deep learning (DL) to identify multiple types of primary origins remains unclear. PURPOSE: To distinguish primary site of BM and identify the best DL models. STUDY TYPE: Retrospective. POPULATION: A total of 449 BM derived from 214 patients (49.5% for female, mean age 58 years) (100 from small cell lung cancer [SCLC], 125 from non-small cell lung cancer [NSCLC], 116 from breast cancer [BC], and 108 from gastrointestinal cancer [GIC]) were included. FIELD STRENGTH/SEQUENCE: A 3-T, T1 turbo spin echo (T1-TSE), T2-TSE, T2FLAIR-TSE, DWI echo-planar imaging (DWI-EPI) and contrast-enhanced T1-TSE (CE T1-TSE). ASSESSMENT: Lesions were divided into training (n = 285, 153 patients), testing (n = 122, 93 patients), and independent testing cohorts (n = 42, 34 patients). Three-dimensional residual network (3D-ResNet), named 3D ResNet6 and 3D ResNet 18, was proposed for identifying the four origins based on single MRI and combined MRI (T1WI + T2-FLAIR + DWI, CE-T1WI + DWI, CE-T1WI + T2WI + DWI). DL model was used to distinguish lung cancer from non-lung cancer; then SCLC vs. NSCLC for lung cancer classification and BC vs. GIC for non-lung cancer classification was performed. A subjective visual analysis was implemented and compared with DL models. Gradient-weighted class activation mapping (Grad-CAM) was used to visualize the model by heatmaps. STATISTICAL TESTS: The area under the receiver operating characteristics curve (AUC) assess each classification performance. RESULTS: 3D ResNet18 with Grad-CAM and AIC showed better performance than 3DResNet6, 3DResNet18 and the radiologist for distinguishing lung cancer from non-lung cancer, SCLC from NSCLC, and BC from GIC. For single MRI sequence, T1WI, DWI, and CE-T1WI performed best for lung cancer vs. non-lung cancer, SCLC vs. NSCLC, and BC vs. GIC classifications. The AUC ranged from 0.675 to 0.876 and from 0.684 to 0.800 regarding the testing and independent testing datasets, respectively. For combined MRI sequences, the combination of CE-T1WI + T2WI + DWI performed better for BC vs. GIC (AUCs of 0.788 and 0.848 on testing and independent testing datasets, respectively), while the combined MRI approach (T1WI + T2-FLAIR + DWI, CE-T1WI + DWI) could not achieve higher AUCs for lung cancer vs. non-lung cancer, SCLC vs. NSCLC. Grad-CAM helped for model visualization by heatmaps that focused on tumor regions. DATA CONCLUSION: DL models may help to distinguish the origins of BM based on MRI data. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
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Neoplasias Encefálicas , Neoplasias de la Mama , Carcinoma de Pulmón de Células no Pequeñas , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Femenino , Persona de Mediana Edad , Imagen de Difusión por Resonancia Magnética/métodos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Estudios Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patologíaRESUMEN
This study aims to develop and validate a deep learning (DL) model to differentiate glioblastoma from single brain metastasis (BM) using conventional MRI combined with diffusion-weighted imaging (DWI). Preoperative conventional MRI and DWI of 202 patients with solitary brain tumor (104 glioblastoma and 98 BM) were retrospectively obtained between February 2016 and September 2022. The data were divided into training and validation sets in a 7:3 ratio. An additional 32 patients (19 glioblastoma and 13 BM) from a different hospital were considered testing set. Single-MRI-sequence DL models were developed using the 3D residual network-18 architecture in tumoral (T model) and tumoral + peritumoral regions (T&P model). Furthermore, the combination model based on conventional MRI and DWI was developed. The area under the receiver operating characteristic curve (AUC) was used to assess the classification performance. The attention area of the model was visualized as a heatmap by gradient-weighted class activation mapping technique. For the single-MRI-sequence DL model, the T2WI sequence achieved the highest AUC in the validation set with either T models (0.889) or T&P models (0.934). In the combination models of the T&P model, the model of DWI combined with T2WI and contrast-enhanced T1WI showed increased AUC of 0.949 and 0.930 compared with that of single-MRI sequences in the validation set, respectively. And the highest AUC (0.956) was achieved by combined contrast-enhanced T1WI, T2WI, and DWI. In the heatmap, the central region of the tumoral was hotter and received more attention than other areas and was more important for differentiating glioblastoma from BM. A conventional MRI-based DL model could differentiate glioblastoma from solitary BM, and the combination models improved classification performance.
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Neoplasias Encefálicas , Aprendizaje Profundo , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patologíaRESUMEN
Rapeseed has the ability to absorb cadmium in the roots and transfer it to aboveground organs, making it a potential species for remediating soil cadmium (Cd) pollution. However, the genetic and molecular mechanisms underlying this phenomenon in rapeseed are still unclear. In this study, a 'cadmium-enriched' parent, 'P1', with high cadmium transport and accumulation in the shoot (cadmium root: shoot transfer ratio of 153.75%), and a low-cadmium-accumulation parent, 'P2', (with a cadmium transfer ratio of 48.72%) were assessed for Cd concentration using inductively coupled plasma mass spectrometry (ICP-MS). An F2 genetic population was constructed by crossing 'P1' with 'P2' to map QTL intervals and underlying genes associated with cadmium enrichment. Fifty extremely cadmium-enriched F2 individuals and fifty extremely low-accumulation F2 individuals were selected based on cadmium content and cadmium transfer ratio and used for bulk segregant analysis (BSA) in combination with whole genome resequencing. This generated a total of 3,660,999 SNPs and 787,034 InDels between these two segregated phenotypic groups. Based on the delta SNP index (the difference in SNP frequency between the two bulked pools), nine candidate Quantitative trait loci (QTLs) from five chromosomes were identified, and four intervals were validated. RNA sequencing of 'P1' and 'P2' in response to cadmium was also performed and identified 3502 differentially expressed genes (DEGs) between 'P1' and 'P2' under Cd treatment. Finally, 32 candidate DEGs were identified within 9 significant mapping intervals, including genes encoding a glutathione S-transferase (GST), a molecular chaperone (DnaJ), and a phosphoglycerate kinase (PGK), among others. These genes are strong candidates for playing an active role in helping rapeseed cope with cadmium stress. Therefore, this study not only sheds new light on the molecular mechanisms of Cd accumulation in rapeseed but could also be useful for rapeseed breeding programs targeting this trait.
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Brassica napus , Cadmio , Humanos , Brassica napus/genética , Fitomejoramiento , Sitios de Carácter Cuantitativo , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: Although eukaryotic initiation factor 6 (eIF6) is a novel therapeutic target, data on its importance in the development of esophageal carcinoma (ESCA) remains limited. This study evaluated the correlation between eIF6 expression and metabolic analysis using fluorine-18 fluorodeoxyglucose (18F-FDG) -Positron emission tomography (PET) and immune gene signatures in ESCA. METHODS: This study employed The Cancer Genome Atlas (TCGA) to analyze the expression and prognostic value of eIF6, as well as its relationship with the immune gene signatures in ESCA patients. The qRT-PCR and Western blot analyses were used to profile the expression of eIF6 in ESCA tissues and different ESCA cell lines. The expression of tumor eIF6 and glucose transporter 1 (GLUT1) was examined using immunohistochemical tools in fifty-two ESCA patients undergoing routine 18F-FDG PET/CT before surgery. In addition, the cellular responses to eIF6 knockdown in human ESCA cells were assessed via the MTS, EdU, flow cytometry and wound healing assays. RESULTS: Our data demonstrated that compared with the normal esophageal tissues, eIF6 expression was upregulated in ESCA tumor tissues and showed a high diagnostic value with an area under curve of 0.825 for predicting ESCA. High eIF6 expression was significantly correlated with shorter overall survival of patients with esophagus adenocarcinoma (p = 0.038), but not in squamous cell carcinoma of the esophagus (p = 0.078). In addition, tumor eIF6 was significantly associated with 18F-FDG PET/CT parameters: maximal and mean standardized uptake values (SUVmax and SUVmean) and total lesion glycolysis (TLG) (rho = 0.458, 0.460, and 0.300, respectively, p < 0.01) as well as GLUT1 expression (rho = 0.453, p < 0.001). A SUVmax cutoff of 18.2 led to prediction of tumor eIF6 expression with an accuracy of 0.755. Functional analysis studies demonstrated that knockdown of eIF6 inhibited ESCA cell growth and migration, and fueled cell apoptosis. Moreover, the Bulk RNA gene analysis revealed a significant inverse association between eIF6 and the tumor-infiltrating immune cells (macrophages, T cells, or Th1 cells) and immunomodulators in the ESCA microenvironment. CONCLUSION: Our study suggested that eIF6 might serve as a potential prognostic biomarker associated with metabolic variability and immune gene signatures in ESCA tumor microenvironment.
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Carcinoma de Células Escamosas , Fluorodesoxiglucosa F18 , Biomarcadores , Transportador de Glucosa de Tipo 1 , Humanos , Factores de Iniciación de Péptidos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Pronóstico , Microambiente TumoralRESUMEN
RATIONALE: Angiogenesis occurs after ischemic injury to skeletal muscle, and enhancing this response has been a therapeutic goal. However, to appropriately deliver oxygen, a precisely organized and exquisitely responsive microcirculation must form. Whether these network attributes exist in a regenerated microcirculation is unknown, and methodologies for answering this have been lacking. OBJECTIVE: To develop 4-dimensional methodologies for elucidating microarchitecture and function of the reconstructed microcirculation in skeletal muscle. METHODS AND RESULTS: We established a model of complete microcirculatory regeneration after ischemia-induced obliteration in the mouse extensor digitorum longus muscle. Dynamic imaging of red blood cells revealed the regeneration of an extensive network of flowing neo-microvessels, which after 14 days structurally resembled that of uninjured muscle. However, the skeletal muscle remained hypoxic. Red blood cell transit analysis revealed slow and stalled flow in the regenerated capillaries and extensive arteriolar-venular shunting. Furthermore, spatial heterogeneity in capillary red cell transit was highly constrained, and red blood cell oxygen saturation was low and inappropriately variable. These abnormalities persisted to 120 days after injury. To determine whether the regenerated microcirculation could regulate flow, the muscle was subjected to local hypoxia using an oxygen-permeable membrane. Hypoxia promptly increased red cell velocity and flux in control capillaries, but in neocapillaries, the response was blunted. Three-dimensional confocal imaging revealed that neoarterioles were aberrantly covered by smooth muscle cells, with increased interprocess spacing and haphazard actin microfilament bundles. CONCLUSIONS: Despite robust neovascularization, the microcirculation formed by regenerative angiogenesis in skeletal muscle is profoundly flawed in both structure and function, with no evidence for normalizing over time. This network-level dysfunction must be recognized and overcome to advance regenerative approaches for ischemic disease.
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Hipoxia/diagnóstico por imagen , Isquemia/diagnóstico por imagen , Microcirculación , Microscopía Confocal/métodos , Microscopía por Video/métodos , Microvasos/diagnóstico por imagen , Músculo Esquelético/irrigación sanguínea , Neovascularización Fisiológica , Animales , Arteriolas/diagnóstico por imagen , Arteriolas/fisiopatología , Capilares/diagnóstico por imagen , Capilares/fisiopatología , Hipoxia de la Célula , Microambiente Celular , Modelos Animales de Enfermedad , Eritrocitos/metabolismo , Miembro Posterior , Hipoxia/sangre , Hipoxia/fisiopatología , Interpretación de Imagen Asistida por Computador , Isquemia/sangre , Isquemia/fisiopatología , Masculino , Ratones Endogámicos C57BL , Microvasos/fisiopatología , Oxígeno/sangre , Flujo Sanguíneo Regional , Factores de Tiempo , Vénulas/diagnóstico por imagen , Vénulas/fisiopatologíaRESUMEN
BACKGROUND: Magnetic resonance (MR) spectroscopy (1H-MRS) has been demonstrated to be useful in grading glioma, but the utility in assessing cellular proliferation activity and prognosis correlated with the expression of minichromosome maintenance protein 2 (MCM2) has not been reported. PURPOSE: To explore the correlation between proton MR spectroscopy parameters (including choline [Cho]/creatine [Cr], N-acetyl aspartate [NAA]/Cr, and Cho/NAA ratios) and the expression of MCM2 and to further evaluate whether 1H-MRS can predict cell proliferative activity and provide prognostic information in high-grade gliomas (HGGs). MATERIAL AND METHODS: Forty-three patients with histopathologically confirmed gliomas were involved in this study. All patients underwent 1H-MRS examination before surgery. Proliferative activity of gliomas was evaluated by MCM2 labeling index (LI). Pearson correlation analysis and empiric receiver operating characteristic (ROC) curves were performed. The Kaplan-Meier method and Cox regression were used for survival analysis. RESULTS: Significant correlation was observed between the Cho/Cr ratio and MCM2 LI ( r = 0.522, P < 0.01); however, there was no correlation between MCM2 LI and the Cho/NAA or NAA/Cr ratios ( r = 0.295, P = 0.55 and r = -0.042, P = 0.788, respectively). According to ROC analysis, MCM2 LI of 50% and Cho/Cr ratio of 2.68 represented the optimized cut-off values, respectively, to distinguish longer or shorter survival than 15 months in HGGs patients. Multivariate analysis revealed that both the Cho/Cr ratio and MCM2 expression were independent prognostic markers. CONCLUSION: Cho/Cr ratio has a potential in predicting the expression of MCM2 and can evaluate cell proliferative activity noninvasively. Both the Cho/Cr ratio and MCM2 expression are independent prognostic markers in patients with HGGs.
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Neoplasias Encefálicas/patología , Proliferación Celular/fisiología , Colina/metabolismo , Creatina/metabolismo , Glioma/patología , Espectroscopía de Resonancia Magnética/métodos , Componente 2 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Adolescente , Adulto , Anciano , Ácido Aspártico/análogos & derivados , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Niño , Femenino , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Componente 2 del Complejo de Mantenimiento de Minicromosoma/genética , Clasificación del Tumor , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. To evaluate the effect of radiotherapy noninvasively, it is vital for oncologists to monitor the effects of X-ray irradiation on glioma cells. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can be used as a biomarker to evaluate apoptosis in glioma cells after X-ray irradiation. In this study, we evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells. METHODS: Cells of the glioma cell lines C6 and U251 were randomly divided into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and 15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA damage. Flow cytometry was performed to measure the cell cycle blockage and apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC-ι (p-PKC-ι) level. 1H NMR spectroscopy was employed to determine the Lac/Cr ratio. RESULTS: The DNA damage increased in a radiation dose-dependent manner (p < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6, p < 0.01; U251, p < 0.05), and the p-PKC-ι level decreased (C6, p < 0.01; U251, p < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level. CONCLUSION: The Lac/Cr ratio decreases with an increase in X-ray irradiation and thus can be used as a biomarker to reflect the effects of X-ray irradiation in glioma cells.
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Apoptosis/efectos de la radiación , Creatina/análisis , Ácido Láctico/análisis , Rayos X , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Puntos de Control del Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Daño del ADN/efectos de la radiación , Electroforesis en Gel de Campo Pulsado , Glioma/metabolismo , Glioma/patología , Humanos , Isoenzimas/metabolismo , Espectroscopía de Resonancia Magnética , Proteína Quinasa C/metabolismo , Análisis de la Célula IndividualRESUMEN
RATIONALE AND OBJECTIVES: Ki67 proliferation index is associated with more aggressive tumor behavior and recurrence of pituitary adenomas (PAs). Recently, radiomics and deep learning have been introduced into the study of pituitary tumors. The present study aimed to investigate the feasibility of predicting the Ki67 proliferation index of PAs using the deep segmentation network and radiomics analysis based on multiparameter MRI. MATERIALS AND METHODS: First, the cfVB-Net autosegmentation model was trained; subsequently, its performance was evaluated in terms of the dice similarity coefficient (DSC). In the present study, 1214 patients were classified into the high Ki67 expression group (HG) and the low Ki67 expression group (LG). Analyses of three classification models based on radiomics features were performed to distinguish HG from LG. Clinical factors, imaging features, and Radscores were collectively used to create a nomogram in order to effectively predict Ki67 expression. RESULTS: The cfVB-Net segmentation model demonstrated good performance (DSC: 0.723-0.930). Overall, 18, 15, and 11 optimal features in contrast-enhanced (CE) T1WI, T1WI, and T2WI were obtained for differentiating between HG and LG, respectively. Notably, the best results were presented in the bagging decision tree when CE T1WI and T1WI were combined (area under the receiver operating characteristic curve: training set, 0.927; validation set, 0.831; and independent testing set, 0.825). In the nomogram, age, Hardy' grade, and Radscores were identified as risk predictors of high Ki67 expression. CONCLUSION: The deep segmentation network and radiomics analysis based on multiparameter MRI exhibited good performance and clinical application value in predicting the expression of Ki67 in PAs.
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Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico por imagen , Radiómica , Antígeno Ki-67 , Imagen por Resonancia Magnética , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Estudios RetrospectivosRESUMEN
This study aims to investigate the feasibility of preoperatively predicting histological subtypes of pituitary neuroendocrine tumors (PitNETs) using machine learning and radiomics based on multiparameter MRI. Patients with PitNETs from January 2016 to May 2022 were retrospectively enrolled from four medical centers. A cfVB-Net network was used to automatically segment PitNET multiparameter MRI. Radiomics features were extracted from the MRI, and the radiomics score (Radscore) of each patient was calculated. To predict histological subtypes, the Gaussian process (GP) machine learning classifier based on radiomics features was performed. Multi-classification (six-class histological subtype) and binary classification (PRL vs. non-PRL) GP model was constructed. Then, a clinical-radiomics nomogram combining clinical factors and Radscores was constructed using the multivariate logistic regression analysis. The performance of the models was evaluated using receiver operating characteristic (ROC) curves. The PitNET auto-segmentation model eventually achieved the mean Dice similarity coefficient of 0.888 in 1206 patients (mean age 49.3 ± SD years, 52% female). In the multi-classification model, the GP of T2WI got the best area under the ROC curve (AUC), with 0.791, 0.801, and 0.711 in the training, validation, and external testing set, respectively. In the binary classification model, the GP of T2WI combined with CE T1WI demonstrated good performance, with AUC of 0.936, 0.882, and 0.791 in training, validation, and external testing sets, respectively. In the clinical-radiomics nomogram, Radscores and Hardy' grade were identified as predictors for PRL expression. Machine learning and radiomics analysis based on multiparameter MRI exhibited high efficiency and clinical application value in predicting the PitNET histological subtypes.
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PURPOSE: To investigate the feasibility of deep learning (DL) based on conventional MRI to differentiate tuberculous spondylitis (TS) from brucellar spondylitis (BS). METHODS: A total of 383 patients with TS (n = 182) or BS (n = 201) were enrolled from April 2013 to May 2023 and randomly divided into training (n = 307) and validation (n = 76) sets. Sagittal T1WI, T2WI, and fat-suppressed (FS) T2WI images were used to construct single-sequence DL models and combined models based on VGG19, VGG16, ResNet18, and DenseNet121 network. The area under the receiver operating characteristic curve (AUC) was used to assess the classification performance. The AUC of DL models was compared with that of two radiologists with different levels of experience. RESULTS: The AUCs based on VGG19, ResNet18, VGG16, and DenseNet121 ranged from 0.885 to 0.973, 0.873 to 0.944, 0.882 to 0.929, and 0.801 to 0.933, respectively, and VGG19 models performed better. The diagnostic efficiency of combined models outperformed single-sequence DL models. The combined model of T1WI, T2WI, and FS T2WI based on VGG19 achieved optimal performance, with an AUC of 0.973. In addition, the performance of all combined models based on T1WI, T2WI, and FS T2WI was better than that of two radiologists (P<0.05). CONCLUSION: The DL models have potential guiding value in the diagnosis of TS and BS based on conventional MRI and provide a certain reference for clinical work.
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Brucelosis , Aprendizaje Profundo , Imagen por Resonancia Magnética , Espondilitis , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Espondilitis/diagnóstico por imagen , Espondilitis/microbiología , Persona de Mediana Edad , Adulto , Brucelosis/diagnóstico por imagen , Diagnóstico Diferencial , Anciano , Estudios de Factibilidad , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Algoritmos , Adulto Joven , Sensibilidad y EspecificidadRESUMEN
RATIONALE AND OBJECTIVES: To develop and validate a deep learning radiomics (DLR) model based on contrast-enhanced computed tomography (CT) to identify the primary source of liver metastases. MATERIALS AND METHODS: In total, 657 liver metastatic lesions, including breast cancer (BC), lung cancer (LC), colorectal cancer (CRC), gastric cancer (GC), and pancreatic cancer (PC), from 428 patients were collected at three clinical centers from January 2018 to October 2023 series. The lesions were randomly assigned to the training and validation sets in a 7:3 ratio. An additional 112 lesions from 61 patients at another clinical center served as an external test set. A DLR model based on contrast-enhanced CT of the liver was developed to distinguish the five pathological types of liver metastases. Stepwise classification was performed to improve the classification efficiency of the model. Lesions were first classified as digestive tract cancer (DTC) and non-digestive tract cancer (non-DTC). DTCs were divided into CRC, GC, and PC and non-DTCs were divided into LC and BC. To verify the feasibility of the DLR model, we trained classical machine learning (ML) models as comparison models. Model performance was evaluated using accuracy (ACC) and area under the receiver operating characteristic curve (AUC). RESULTS: The classification model constructed by the DLR algorithm showed excellent performance in the classification task compared to ML models. Among the five categories task, highest ACC and average AUC were achieved at 0.563 and 0.796 in the validation set, respectively. In the DTC and non-DTC and the LC and BC classification tasks, AUC was achieved at 0.907 and 0.809 and ACC was achieved at 0.843 and 0.772, respectively. In the CRC, GC, and PC classification task, ACC and average AUC were the highest, at 0.714 and 0.811, respectively. CONCLUSION: The DLR model is an effective method for identifying the primary source of liver metastases.
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Land-ocean interactions greatly impact the evolution of coastal life on earth. However, the ancient geological forces and genetic mechanisms that shaped evolutionary adaptations and allowed microorganisms to inhabit coastal brackish waters remain largely unexplored. In this study, we infer the evolutionary trajectory of the ubiquitous heterotrophic archaea Poseidoniales (Marine Group II archaea) presently occurring across global aquatic habitats. Our results show that their brackish subgroups had a single origination, dated to over 600 million years ago, through the inversion of the magnesium transport gene corA that conferred osmotic-stress tolerance. The subsequent loss and gain of corA were followed by genome-wide adjustment, characterized by a general two-step mode of selection in microbial speciation. The coastal family of Poseidoniales showed a rapid increase in the evolutionary rate during and in the aftermath of the Cryogenian Snowball Earth (â¼700 million years ago), possibly in response to the enhanced phosphorus supply and the rise of algae. Our study highlights the close interplay between genetic changes and ecosystem evolution that boosted microbial diversification in the Neoproterozoic continental margins, where the Cambrian explosion of animals soon followed.
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The aim of this study was to investigate the feasibility of deep learning (DL) based on multiparametric MRI to differentiate the pathological subtypes of brain metastasis (BM) in lung cancer patients. This retrospective analysis collected 246 patients (456 BMs) from five medical centers from July 2016 to June 2022. The BMs were from small-cell lung cancer (SCLC, n = 230) and non-small-cell lung cancer (NSCLC, n = 226; 119 adenocarcinoma and 107 squamous cell carcinoma). Patients from four medical centers were assigned to training set and internal validation set with a ratio of 4:1, and we selected another medical center as an external test set. An attention-guided residual fusion network (ARFN) model for T1WI, T2WI, T2-FLAIR, DWI, and contrast-enhanced T1WI based on the ResNet-18 basic network was developed. The area under the receiver operating characteristic curve (AUC) was used to assess the classification performance. Compared with models based on five single-sequence and other combinations, a multiparametric MRI model based on five sequences had higher specificity in distinguishing BMs from different types of lung cancer. In the internal validation and external test sets, AUCs of the model for the classification of SCLC and NSCLC brain metastasis were 0.796 and 0.751, respectively; in terms of differentiating adenocarcinoma from squamous cell carcinoma BMs, the AUC values of the prediction models combining the five sequences were 0.771 and 0.738, respectively. DL together with multiparametric MRI has discriminatory feasibility in identifying pathology type of BM from lung cancer.
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Neoplasias Encefálicas , Aprendizaje Profundo , Neoplasias Pulmonares , Imagen por Resonancia Magnética , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Imagen por Resonancia Magnética/métodos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/secundario , Adulto , Interpretación de Imagen Asistida por Computador/métodos , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/secundario , Estudios de Factibilidad , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Curva ROCRESUMEN
IL-36 is known to mediate inflammation and fibrosis. Nevertheless, IL-36 signalling axis has also been implicated in cancer, although understanding of exact contribution of IL-36 to cancer progression is very limited, partly due to existence of multiple IL-36 ligands with agonistic and antagonistic function. Here we explored the role of IL-36 in oral squamous cell carcinoma (OSCC). Firstly, we analyzed expression of IL-36 ligands and receptor and found that the expression of IL-36γ was significantly higher in head and neck cancer (HNSCC) than that of normal tissues, and that the high expression of IL-36γ predicted poor clinical outcomes. Secondly, we investigated the direct effect of IL-36γ on OSCC cells and found that IL-36γ stimulated proliferation of OSCC cells with high expression of IL-36R expression. Interestingly, IL-36γ also promoted migration of OSCC cells with low to high IL-36R expression. Critically, both proliferation and migration of OSCC cells induced by IL-36γ were abrogated by anti-IL-36R mAb. Fittingly, RNA sequence analysis revealed that IL-36γ regulated genes involved in cell cycle and cell division. In summary, our results showed that IL-36γ can be a tumor-promoting factor, and targeting of IL-36R signalling may be a beneficial targeted therapy for patients with abnormal IL-36 signalling.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Interleucina-1/metabolismo , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Proliferación Celular , Línea Celular TumoralRESUMEN
A considerable amount of particulate carbon produced by oceanic photosynthesis is exported to the deep-sea by the "gravitational pump" (~6.8 to 7.7 Pg C/year), sequestering it from the atmosphere for centuries. How particulate organic carbon (POC) is transformed during export to the deep sea however is not well understood. Here, we report that dominant suspended prokaryotes also found in sinking particles serve as informative tracers of particle export processes. In a three-year time series from oceanographic campaigns in the Pacific Ocean, upper water column relative abundances of suspended prokaryotes entrained in sinking particles decreased exponentially from depths of 75 to 250 m, conforming to known depth-attenuation patterns of carbon, energy, and mass fluxes in the epipelagic zone. Below ~250 m however, the relative abundance of suspended prokaryotes entrained in sinking particles increased with depth. These results indicate that microbial entrainment, colonization, and sinking particle formation are elevated at mesopelagic and bathypelagic depths. Comparison of suspended and sinking particle-associated microbes provides information about the depth-variability of POC export and biotic processes, that is not evident from biogeochemical data alone.