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Reasonable application of nitrogen fertilizer can improve the yield and quality of tea. This study used Jin Xuan as the tested variety and applied nitrogen fertilizer at rates of 0 kg/ha (N0), 150 kg/ha (N150), 300 kg/ha (N300), and 450 kg/ha (N450) in the summer and autumn seasons to analyze the effects of nitrogen application on the quality components and gene expression of tea leaves. The results showed that the N150 treatment significantly increased total polyphenols (TP), total catechins (TC), and caffeine contents, with the most significant increase observed in the content of six monomers of catechins (EGCG, ECG, EGC, GCG, GC, and EC) in the summer. The N300 treatment significantly increased TP and AA contents in the autumn while decreasing TC content. Additionally, the N300 treatment significantly increased caffeine and theanine contents in the autumn. Notably, the N300 treatment significantly increased both summer and autumn tea yields. Multivariate statistical analysis showed that TPs, AAs, TCs, EGC, and caffeine were key factors affecting the quality of Jin Xuan. Furthermore, the N150 treatment upregulated the expression of the phenylalanine ammonia-lyase (PAL) gene, which may increase the accumulation of catechins. In conclusion, it is recommended to apply 150 kg/ha of nitrogen fertilizer in the summer and 300 kg/ha of nitrogen fertilizer in the autumn. This recommendation provides a theoretical basis for improving the quality and yield of tea leaves in summer and autumn.
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Objective.This study aims to address the challenges of imbalanced heartbeat classification using electrocardiogram (ECG). In this proposed novel deep-learning method, the focus is on accurately identifying minority classes in conditions characterized by significant imbalances in ECG data.Approach.We propose a feature fusion neural network enhanced by a dynamic minority-biased batch weighting loss function. This network comprises three specialized branches: the complete ECG data branch for a comprehensive view of ECG signals, the local QRS wave branch for detailed features of the QRS complex, and theRwave information branch to analyzeRwave characteristics. This structure is designed to extract diverse aspects of ECG data. The dynamic loss function prioritizes minority classes while maintaining the recognition of majority classes, adjusting the network's learning focus without altering the original data distribution. Together, this fusion structure and adaptive loss function significantly improve the network's ability to distinguish between various heartbeat classes, enhancing the accuracy of minority class identification.Main results.The proposed method demonstrated balanced performance within the MIT-BIH dataset, especially for minority classes. Under the intra-patient paradigm, the accuracy, sensitivity, specificity, and positive predictive value for Supraventricular ectopic beat were 99.63%, 93.62%, 99.81%, and 92.98%, respectively, and for Fusion beat were 99.76%, 85.56%, 99.87%, and 84.16%, respectively. Under the inter-patient paradigm, these metrics were 96.56%, 89.16%, 96.84%, and 51.99%for Supraventricular ectopic beat, and 96.10%, 77.06%, 96.25%, and 13.92%for Fusion beat, respectively.Significance.This method effectively addresses the class imbalance in ECG datasets. By leveraging diverse ECG signal information and a novel loss function, this approach offers a promising tool for aiding in the diagnosis and treatment of cardiac conditions.
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Eletrocardiografia , Frequência Cardíaca , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , Humanos , Frequência Cardíaca/fisiologia , Aprendizado ProfundoRESUMO
Industrial process monitoring is a critical application of multivariate time-series (MTS) anomaly detection, especially crucial for safety-critical systems such as nuclear power plants (NPPs). However, some current data-driven process monitoring approaches may not fully capitalize on the temporal-spatial correlations inherent in operational MTS data. Particularly, asynchronous time-lagged correlations may exist among variables in actual NPPs, which further complicates this challenge. In this work, a reconstruction-based MTS anomaly detection approach based on a temporal-spatial transformer is proposed. It employs a two-stage temporal-spatial attention mechanism combined with a multi-scale strategy to learn the dependencies within normal operational data at various scales, thereby facilitating the extraction of temporal-spatial correlations from asynchronous MTS. Experiments on simulated datasets and real NPP datasets demonstrate that the proposed model possesses stronger feature learning capabilities, as evidenced by its improved performance in signal reconstruction and anomaly detection for asynchronous MTS data. Moreover, the proposed TS-Trans model enables earlier detection of anomalous events, which holds significant importance for enhancing operational safety and reducing potential losses in NPPs.
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BACKGROUND: Grade 4 glioma is the most aggressive and currently incurable brain tumor with a median survival of one year in adult patients. Elucidating novel transcriptomic and epigenetic contributors to the molecular heterogeneity underlying its aggressiveness may lead to improved clinical outcomes. METHODS: To identify grade 4 glioma -associated 5-hydroxymethylcytosine (5hmC) and transcriptomic features as well as their cross-talks, genome-wide 5hmC and transcriptomic profiles of tissue samples from 61 patients with grade 4 gliomas and 9 normal controls were obtained for differential and co-regulation/co-modification analyses. Prognostic models on overall survival based on transcriptomic features and the 5hmC modifications summarized over genic regions (promoters, gene bodies) and brain-derived histone marks were developed using machine learning algorithms. RESULTS: Despite global reduction, the majority of differential 5hmC features showed higher modification levels in grade 4 gliomas as compared to normal controls. In addition, the bi-directional correlations between 5hmC modifications over promoter regions or gene bodies and gene expression were greatly disturbed in grade 4 gliomas regardless of IDH1 mutation status. Phenotype-associated co-regulated 5hmC-5hmC modules and 5hmC-mRNA modules not only are enriched with different molecular pathways that are indicative of the pathogenesis of grade 4 gliomas, but also are of prognostic significance comparable to IDH1 mutation status. Lastly, the best-performing 5hmC model can predict patient survival at a much higher accuracy (c-index = 74%) when compared to conventional prognostic factor IDH1 (c-index = 57%), capturing the molecular characteristics of tumors that are independent of IDH1 mutation status and gene expression-based molecular subtypes. CONCLUSIONS: The 5hmC-based prognostic model could offer a robust tool to predict survival in patients with grade 4 gliomas, potentially outperforming existing prognostic factors such as IDH1 mutations. The crosstalk between 5hmC and gene expression revealed another layer of complexity underlying the molecular heterogeneity in grade 4 gliomas, offering opportunities for identifying novel therapeutic targets.
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Neoplasias Encefálicas , Glioma , Humanos , Transcriptoma , Glioma/patologia , Prognóstico , Neoplasias Encefálicas/patologia , Mutação , Epigênese Genética , Isocitrato Desidrogenase/genéticaRESUMO
BACKGROUND: Current intensity-modulated radiation therapy (IMRT) treatment planning is still a manual and time/resource consuming task, knowledge-based planning methods with appropriate predictions have been shown to enhance the plan quality consistency and improve planning efficiency. This study aims to develop a novel prediction framework to simultaneously predict dose distribution and fluence for nasopharyngeal carcinoma treated with IMRT, the predicted dose information and fluence can be used as the dose objectives and initial solution for an automatic IMRT plan optimization scheme, respectively. METHODS: We proposed a shared encoder network to simultaneously generate dose distribution and fluence maps. The same inputs (three-dimensional contours and CT images) were used for both dose distribution and fluence prediction. The model was trained with datasets of 340 nasopharyngeal carcinoma patients (260 cases for training, 40 cases for validation, 40 cases for testing) treated with nine-beam IMRT. The predicted fluence was then imported back to treatment planning system to generate the final deliverable plan. Predicted fluence accuracy was quantitatively evaluated within projected planning target volumes in beams-eye-view with 5 mm margin. The comparison between predicted doses, predicted fluence generated doses and ground truth doses were also conducted inside patient body. RESULTS: The proposed network successfully predicted similar dose distribution and fluence maps compared with ground truth. The quantitative evaluation showed that the pixel-based mean absolute error between predicted fluence and ground truth fluence was 0.53% ± 0.13%. The structural similarity index also showed high fluence similarity with values of 0.96 ± 0.02. Meanwhile, the difference in the clinical dose indices for most structures between predicted dose, predicted fluence generated dose and ground truth dose were less than 1 Gy. As a comparison, the predicted dose achieved better target dose coverage and dose hot spot than predicted fluence generated dose compared with ground truth dose. CONCLUSION: We proposed an approach to predict 3D dose distribution and fluence maps simultaneously for nasopharyngeal carcinoma patients. Hence, the proposed method can be potentially integrated in a fast automatic plan generation scheme by using predicted dose as dose objectives and predicted fluence as a warm start.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Carcinoma Nasofaríngeo/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Nasofaríngeas/radioterapiaRESUMO
Synthesizing computed tomography (CT) images from magnetic resonance imaging (MRI) data can provide the necessary electron density information for accurate dose calculation in the treatment planning of MRI-guided radiation therapy (MRIgRT). Inputting multimodality MRI data can provide sufficient information for accurate CT synthesis: however, obtaining the necessary number of MRI modalities is clinically expensive and time-consuming. In this study, we propose a multimodality MRI synchronous construction based deep learning framework from a single T1-weight (T1) image for MRIgRT synthetic CT (sCT) image generation. The network is mainly based on a generative adversarial network with sequential subtasks of intermediately generating synthetic MRIs and jointly generating the sCT image from the single T1 MRI. It contains a multitask generator and a multibranch discriminator, where the generator consists of a shared encoder and a splitted multibranch decoder. Specific attention modules are designed within the generator for feasible high-dimensional feature representation and fusion. Fifty patients with nasopharyngeal carcinoma who had undergone radiotherapy and had CT and sufficient MRI modalities scanned (5550 image slices for each modality) were used in the experiment. Results showed that our proposed network outperforms state-of-the-art sCT generation methods well with the least MAE, NRMSE, and comparable PSNR and SSIM index measure. Our proposed network exhibits comparable or even superior performance than the multimodality MRI-based generation method although it only takes a single T1 MRI image as input, thereby providing a more effective and economic solution for the laborious and high-cost generation of sCT images in clinical applications.
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Aprendizado Profundo , Humanos , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal , Planejamento da Radioterapia Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodosRESUMO
Epigenetic modifications play critical roles in gene regulation and disease pathobiology. Highly sensitive enabling technologies, including microarray- and sequencing-based approaches have allowed genome-wide profiling of cytosine modifications in DNAs in clinical samples to facilitate discovery of epigenetic biomarkers for disease diagnosis and prognosis. Historically, many previous studies, however, did not distinguish the most investigated 5-methylcytosines (5mC) from other modified cytosines, especially the biochemically stable 5-hydroxymethylcytosines (5hmC), which have been shown to have a distinct genomic distribution and regulatory role from 5mC. Notably, during the past several years, the 5hmC-Seal, a highly sensitive chemical labeling technique, has been demonstrated to be a powerful tool for genome-wide profiling of 5hmC in clinically feasible biospecimens (e.g. a few milliliter of plasma or serum). The 5hmC-Seal technique has been utilized by our team in biomarker discovery for human cancers and other complex diseases using circulating cell-free DNA (cfDNA), as well as the characterization of the first 5hmC Human Tissue Map. Convenient access to the accumulating 5hmC-Seal data will allow the research community to validate and re-use these results, potentially providing novel insights into epigenetic contribution to a range of human diseases. Here we introduce the PETCH-DB, an integrated database that was implemented to provide 5hmC-related results generated using the 5hmC-Seal technique. We aim the PETCH-DB to be a central portal, which will be available to the scientific community with regularly updated 5hmC data in clinical samples to reflect current advances in this field. Database URL http://petch-db.org/.
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5-Metilcitosina , Pesquisa Biomédica , Humanos , Citosina , Bases de Dados FactuaisRESUMO
Epigenetic modifications play critical roles in gene regulation and disease pathobiology. Highly sensitive enabling technologies, including microarray- and sequencing-based approaches have allowed genome-wide profiling of cytosine modifications in DNAs in clinical samples to facilitate discovery of epigenetic biomarkers for disease diagnosis and prognosis. Historically, many previous studies, however, did not distinguish the most investigated 5-methylcytosines (5mC) from other modified cytosines, especially the biochemically stable 5-hydroxymethylcytosines (5hmC), which have been shown to have a distinct genomic distribution and regulatory role from 5mC. Notably, during the past several years, the 5hmC-Seal, a highly sensitive chemical labeling technique, has been demonstrated to be a powerful tool for genome-wide profiling of 5hmC in clinically feasible biospecimens (e.g. a few milliliter of plasma or serum). The 5hmC-Seal technique has been utilized by our team in biomarker discovery for human cancers and other complex diseases using circulating cell-free DNA (cfDNA), as well as the characterization of the first 5hmC Human Tissue Map. Convenient access to the accumulating 5hmC-Seal data will allow the research community to validate and re-use these results, potentially providing novel insights into epigenetic contribution to a range of human diseases. Here we introduce the PETCH-DB, an integrated database that was implemented to provide 5hmC-related results generated using the 5hmC-Seal technique. We aim the PETCH-DB to be a central portal, which will be available to the scientific community with regularly updated 5hmC data in clinical samples to reflect current advances in this field. Database URL http://petch-db.org/.
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5-Metilcitosina , Pesquisa Biomédica , Humanos , Citosina , Bases de Dados FactuaisRESUMO
Asthma is a serious global public health concern. Airway neutrophilic inflammation is closely related to severe asthma, for which effective and safe therapies remain to be developed. Here we report nanotherapies capable of simultaneously regulating multiple target cells relevant to the pathogenesis of neutrophilic asthma. A nanotherapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effectively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells after intravenous or inhalation delivery, thereby ameliorating asthmatic symptoms and attenuating pulmonary neutrophilic inflammation as well as reducing airway hyperresponsiveness, remodeling, and mucus production. Surface engineering via neutrophil cell membrane further enhanced targeting and therapeutic effects of LaCD NP. Mechanistically, LaCD NP can inhibit the recruitment and activation of neutrophils, especially reducing the neutrophil extracellular traps formation and NLRP3 inflammasome activation in neutrophils. Also, LaCD NP can suppress macrophage-mediated pro-inflammatory responses and prevent airway epithelial cell death and smooth muscle cell proliferation, by mitigating neutrophilic inflammation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Consequently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases.
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Spinal cord injury (SCI) is a devastating neurological disorder characterized by high morbidity and disability. However, there is still a lack of effective treatments for it. The identification of drugs that promote autophagy and inhibit apoptosis in neurons is critical for improving patient outcomes following SCI. Previous studies have shown that increasing the activity of silent information regulator 1 (SIRT1) and downstream protein AMP-activated protein kinase (AMPK) in rat models of SCI is highly neuroprotective. Oxymatrine (OMT), a quinolizidine alkaloid, has exhibited neuroprotective effects in various central nervous system (CNS) diseases. However, its explicit effect and molecular mechanism in SCI are still unclear. Herein, we aimed to investigate the therapeutic effects of OMT and explore the potential role of autophagy regulation following SCI in rats. A modified compressive device (weight 35 g, time 5 min) was applied to induce moderate SCI in all groups except the sham group. After treatment with drugs or vehicle (saline), our results indicated that OMT treatment significantly reduced the lesion size, promoted survival of motor neurons, and subsequently attenuated motor dysfunction following SCI in rats. OMT significantly enhanced autophagy activity, inhibited apoptosis in neurons, and increased SIRT1 and p-AMPK expression levels. Interestingly, these effects of OMT on SCI were partially prevented by co-treatment with SIRT1 inhibitor EX527. Furthermore, combining OMT with the potent autophagy inhibitor chloroquine (CQ) could effectively abolish its promotion of autophagic flux. Taken together, these data revealed that OMT exerts a neuroprotective role in functional recovery against SCI in rats, and these effects are potentially associated with OMT-induced activation of autophagy via the SIRT1/AMPK signaling pathway.
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Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Ratos , Animais , Ratos Sprague-Dawley , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 1/metabolismo , Traumatismos da Medula Espinal/patologia , Autofagia , Neurônios Motores/metabolismo , Apoptose , Medula Espinal/patologia , Recuperação de Função FisiológicaRESUMO
Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.
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High potency and safe therapies are still required for ischemic stroke, which is a leading cause of global death and disability. Herein, a reactive oxygen species (ROS)-responsive, transformable, and triple-targeting dl-3-n-butylphthalide (NBP) nanotherapy was developed for ischemic stroke. To this end, a ROS-responsive nanovehicle (OCN) was first constructed using a cyclodextrin-derived material, which showed considerably enhanced cellular uptake in brain endothelial cells due to notably reduced particle size, morphological transformation, and surface chemistry switching upon triggering via pathological signals. Compared to a nonresponsive nanovehicle, this ROS-responsive and transformable nanoplatform OCN exhibited a significantly higher brain accumulation in a mouse model of ischemic stroke, thereby affording notably potentiated therapeutic effects for the nanotherapy derived from NBP-containing OCN. For OCN decorated with a stroke-homing peptide (SHp), we found significantly increased transferrin receptor-mediated endocytosis, in addition to the previously recognized targeting capability to activated neurons. Consistently, the engineered transformable and triple-targeting nanoplatform, i.e., SHp-decorated OCN (SON), displayed a more efficient distribution in the injured brain in mice with ischemic stroke, showing considerable localization in endothelial cells and neurons. Furthermore, the finally formulated ROS-responsive transformable and triple-targeting nanotherapy (NBP-loaded SON) demonstrated highly potent neuroprotective activity in mice, which outperformed the SHp-deficient nanotherapy at a 5-fold higher dose. Mechanistically, our bioresponsive, transformable, and triple-targeting nanotherapy attenuated the ischemia/reperfusion-induced endothelial permeability and improved dendritic remodeling and synaptic plasticity of neurons in the injured brain tissue, thereby promoting much better functional recovery, which were achieved by efficiently enhancing NBP delivery to the ischemic brain tissue, targeting injured endothelial cells and activated neurons/microglial cells, and normalizing the pathological microenvironment. Moreover, preliminary studies indicated that the ROS-responsive NBP nanotherapy displayed a good safety profile. Consequently, the developed triple-targeting NBP nanotherapy with desirable targeting efficiency, spatiotemporally controlled drug release performance, and high translational potential holds great promise for precision therapy of ischemic stroke and other brain diseases.
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Isquemia Encefálica , AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Camundongos , Animais , Espécies Reativas de Oxigênio/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Células Endoteliais , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
PURPOSE: We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy. METHODS AND MATERIALS: A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the quantitative analyses of normal tissue effects in the clinic and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test. RESULTS: The radiomics and dosiomics signatures were constructed based on 30 selected computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P <.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, D1cc, and age had favorable performance, with C-index values of 0.776, 0.811, 0.805, and 0.794 in the training, validation, prospective test, and external test cohorts, respectively, which were better than those of the quantitative analyses of normal tissue effects in the clinic model and Wen's model (all P <.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P <.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P > .05). Two simulated plans with the same dose-volume histogram but different dose distributions had different TLI-free survival rates predicted by dosiomics risk model (all P ≤ .002). CONCLUSIONS: The dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity modulated radiation therapy.
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Neoplasias Nasofaríngeas , Humanos , Estudos Prospectivos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Estudos RetrospectivosRESUMO
The correlation between empathy and customer responses may be a key to solve the problem of classical furniture advertising design. To explore the relationship between empathy and consumer purchasing response, this study proposes a model of dual path mechanism of empathy influencing consumer purchase intentions in classical furniture through advertising design related to furniture brand Tanjuyuan. The results not only prove the hypotheses, but also indicate that: (1) cultural empathy and empathy fusion have a more significant impact on consumers' purchase intention than practical empathy; (2) cultural empathy plays a dominant role in influencing consumers' purchase intention; (3) empathy fusion is a key mediator between cultural empathy and practical empathy in influencing consumers' purchase intention. These findings provide issues for subsequent research from various perspectives, such as enhancing the practical perceptions of consumers of classical furniture products, cultural value perceptions, and the interdisciplinary application of empathy.
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AIMS: This work investigates the effects and mechanisms of inhibiting TRPC6 (a non-selective cation channel) downregulation on rat astrocyte activation and proliferation following spinal cord injury (SCI) by suppressing AQP4 expression. We used HYP9 (TRPC6-specific agonist) and TGN-020 (AQP4-specific inhibitor) to explore the relationship between TRPC6 and AQP4 and their probable protective effects on SCI. METHODS: In a rat SCI model, we randomly assigned female Sprague-Dawley rats into the following four groups: Sham, SCI, SCI+HYP9, and SCI+TGN-020. Western blotting and immunofluorescence staining were used to determine protein expression among groups following SCI. TUNEL and immunofluorescence staining were used to identify changes in the rate of apoptosis and the fraction of surviving neurons after SCI. The Basso-Beattie-Bresnahan open-field locomotor scale was used to identify changes in motor function after SCI. In vitro astrocyte scratch model, we first used the CCK8 assay to test the effects of varying doses of HYP9 or TGN-020 on astrocytes and then split the astrocytes into four groups: Con, Scratch, Scratch+HYP9, and Scratch+TGN-020. Western blotting and immunofluorescence were used to identify changes in the expression of target proteins. RESULTS: In vivo and in vitro models, SCI dramatically decreased TRPC6 while considerably upregulating AQP4, glial fibrillary acidic protein (GFAP), and proliferating cell nuclear antigen (PCNA) expression. However, HYP9 or TGN-020 significantly suppressed activation of astrocytes, promoted neurons survival in the anterior horn of the spinal cords, and benefited the recovery of motor function in the hind limbs of rats following SCI. Interestingly, TRPC6 agonists dramatically suppressed AQP4 overexpression, indicating that the probable mechanism of HYP9 benefiting alleviation of SCI may be connected to AQP4 inhibition and astrocyte activation and proliferation reduction. CONCLUSION: we discovered for the first time that HYP9 inhibits astrocyte activation and proliferation by inhibiting AQP4 in SCI rats in vivo and in vitro models and that it preserves neuronal survival and functional recovery after SCI.
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Astrócitos , Traumatismos da Medula Espinal , Animais , Feminino , Ratos , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Proliferação de Células/fisiologia , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Canais de Cátion TRPC/metabolismo , Canal de Cátion TRPC6/metabolismo , Regulação para CimaRESUMO
PURPOSE: Microvascular decompression (MVD) surgery is the only potential curative method for hemifacial spasm (HFS). Little attention is paid to those recurrent/residual HFS cases. We want to study the potential etiology of those recurrent/residual HFS cases and evaluate the value of reoperation. METHODS: We retrospectively reviewed reoperation hemifacial spasm patients in our hospital. Intraoperative videos or images were carefully reviewed, and the etiology of recurrent/residual HFS is roughly divided into three categories. Intraoperative findings, surgical outcomes, and complications were carefully studied to assess the value of reoperation for recurrent/residual HFS patients. RESULTS: A total of 28 cases were included in our case series. Twenty-three of them are recurrent HFS cases, and 5 of them are residual HFS cases. The mean follow-up duration is 24.96 months. There are seventeen patients with missed culprit vessels or insufficient decompression of root exit zone (REZ), eight patients with Teflon adhesion, and three patients with improper application of decompression materials in our case series. The final reoperation outcome with 17 excellent, seven good, and four fair, respectively. Eight (28.57%) of them experienced long-term complications after reoperation. CONCLUSION: Re-operation for recurrent/residual HFS is an effective therapy and can achieve a higher cure rate. However, the complication rate is higher compared to the first MVD surgery. Accurately identifying REZ and proper decompression strategies to deal with the culprit vessels are very important for surgical success. TRIAL REGISTRATION NUMBER: UIN: researchregistry7603. Date of registration: Jan. 31st, 2022 "retrospectively registered".
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Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Humanos , Espasmo Hemifacial/cirurgia , Espasmo Hemifacial/etiologia , Cirurgia de Descompressão Microvascular/efeitos adversos , Cirurgia de Descompressão Microvascular/métodos , Reoperação/efeitos adversos , Progressão da Doença , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Background: Gliomas are the most malignant central nervous system tumors. With the development of sequencing technology, more potential biomarkers related to the treatment, prognosis, and molecular classification of glioma have been identified. Here, we intend to investigate the potential biological function and clinical value of a new biomarker in glioma. Methods: KDELR1 expression data and the corresponding clinical information were downloaded from public databases and then preprocessed using R language. Correlation, Kaplan-Meier survival, and Cox regression analyses were performed to explore the clinical significance of KDELR1 in glioma patients. Furthermore, the immune infiltration and microenvironment parameters were evaluated via TIMER and CIBERSORT. Immunohistochemistry was conducted to confirm the KDELR1 expression and its correlation with immunity infiltration and prognosis. Results: KDELR1 was upregulated in glioma samples compared with normal brain tissues, and its expression was significantly correlated with age, the World Health Organization (WHO) grade, recurrence, necrosis, microvascular proliferation, molecular classification, isocitrate dehydrogenase (IDH) mutation, and 1p/19q codeletion status. In addition, survival analysis showed that glioma patients with KDELR1 overexpression had shorter overall survival (OS) and disease-free survival times, and Cox regression analysis revealed that KDELR1 acted as an independent prognostic factor of OS in glioma patients. Gene set enrichment analysis indicated a significant enrichment of metabolism-associated pathways. KDELR1 expression was positively associated with immune infiltration (including infiltration by CD8+ T cells, CD4+ T cells, macrophages, and so on) and microenvironment parameters (including stromal, immune, and ESTIMATE scores) in gliomas. The expression of KDELR1 and its correlation with the tumor grade and prognosis were confirmed by immunohistochemistry in clinical samples (n = 119, P < 0.05). Conclusions: Taken together, these findings suggest that KDELR1 is correlated with the tumor grade, molecular classifications, and immune infiltration; highlighting that KDELR1 is a novel and promising biomarker for molecular classification, treatment, and prognostic assessment may further indicate the treating effect of immune therapy.
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Objective: The surgical strategy for falcotentorial junction tumors remains complex. Different approaches are selected according to the location and growth pattern of the tumor and the operator's experience. This report reviews our single-institution experience in the surgical management of falcotentorial junction tumors. Methods: We retrospectively reviewed the clinical and imaging data, surgical strategy, and follow-up outcomes of 49 patients treated from 2007 to 2020. Result: All 49 patients (12 male, 37 female, mean age: 56.3 ± 11.3 years) underwent safe tumor resection. The most common complaints were headache (43%), dizziness (39%), and unstable gait (16%). Thirty percent of the tumors showed calcification, and the computed tomography scans revealed hydrocephalus in 36% of the patients. On magnetic resonance imaging, 43% of the tumors were unilateral. According to the Asari classification, the tumors were divided into inferior (16%), superior (29%), anterior (22%), and posterior (33%) types. The occipital interhemispheric approach (88%) and supracerebellar-infratentorial approach (10%) were primarily used to reach the tumors. The pathology examination results revealed that 85.7% of the tumors were meningioma and 14.3% were hemangiopericytoma. Of the 49 patients, 15 achieved a Simpson grade I resection, and 29 achieved a Simpson grade II resection. The follow-up rate was 77.6% (38/45); 94.7% of patients (36/38) achieved a favorable outcome, and 9 experienced tumor recurrences. Conclusion: Surgical approach selection depends on the growth characteristics of the tumor and the degree of venous or sinus involvement. The occipital interhemispheric approach is the most commonly used and safest approach for falcotentorial junction tumors with multiple brain pressure control assistance techniques.
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Objective. To present a transformer-based UNet model (TransDose) for fast and accurate dose calculation for magnetic resonance-linear accelerators (MR-LINACs).Approach. A 2D fluence map from each beam was first projected into a 3D fluence volume and then fed into the TransDose model together with patient density volume and output predicted beam dose. The proposed TransDose model combined a 3D residual UNet with a transformer encoder, where convolutional layers extracted the volumetric spatial features, and the transformer encoder processed the long-range dependencies in a global space. Ninety-eight cases with four tumor sites (brain, nasopharynx, lung, and rectum) treated with fixed-beam intensity-modulated radiotherapy were included in the dataset; 78 cases were used for model training and validation; and 20 cases were used for testing. The ground-truth beam doses were calculated with Monte Carlo (MC) simulations within 1% statistical uncertainty and magnetic field strengthB = 1.5 T in the superior and inferior direction. Beam angles from the training and validation datasets were rotated 2-5 times, and doses were recalculated to augment the datasets.Results. The dose-volume histograms and indices between the predicted and MC doses showed good consistency. The average 3Dγ-passing rates (3%/2 mm, for dose regions above 10% of maximum dose) were 99.13 ± 0.89% (brain), 98.31 ± 1.92% (nasopharynx), 98.74 ± 0.70% (lung), and 99.28 ± 0.25% (rectum). The average dose calculation time, which included the fluence projection and model prediction, was less than 310 ms for each beam.Significance. We successfully developed a transformer-based UNet dose calculation model-TransDose in magnetic fields. Its accuracy and efficiency indicated its potential for use in online adaptive plan optimization for MR-LINACs.
Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Método de Monte Carlo , Aceleradores de Partículas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodosRESUMO
BACKGROUND: Early detection of breast cancer lung metastasis remains highly challenging, due to few metastatic cancer cells at an early stage. Herein we propose a new strategy for early diagnosis of lung metastasis of breast cancer by luminescence imaging of pulmonary neutrophil infiltration via self-illuminating nanoprobes. METHODS: Luminescent nanoparticles (LAD NPs) were engineered using a biocompatible, neutrophil-responsive self-illuminating cyclodextrin material and an aggregation-induced emission agent. The chemiluminescence resonance energy transfer (CRET) effect and luminescence properties of LAD NPs were fully characterized. Using mouse peritoneal neutrophils, in vitro luminescence properties of LAD NPs were thoroughly examined. In vivo luminescence imaging and correlation analyses were performed in mice inoculated with 4T1 cancer cells. Moreover, an active targeting nanoprobe was developed by surface decoration of LAD NPs with a neutrophil-targeting peptide, which was also systemically evaluated by in vitro and in vivo studies. RESULTS: LAD NPs can generate long-wavelength and persistent luminescence due to the CRET effect. In a mouse model of 4T1 breast cancer lung metastasis, we found desirable correlation between neutrophils and tumor cells in the lungs, demonstrating the effectiveness of early imaging of the pre-metastatic niche by the newly developed LAD NPs. The active targeting nanoprobe showed further enhanced luminescence imaging capability for early detection of pulmonary metastasis. Notably, the targeting nanoprobe-based luminescence imaging strategy remarkably outperformed PET/CT imaging modalities in the examined mouse model. Also, preliminary tests demonstrated good safety of LAD NPs. CONCLUSIONS: The neutrophil-targeting imaging strategy based on newly developed luminescence nanoparticles can serve as a promising modality for early diagnosis of lung metastasis of breast cancers.