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[This corrects the article DOI: 10.3389/fcell.2021.793073.].
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Achieving high-luminescence organic light-emitting devices (OLEDs) with narrowband emission and high color purity is important in various optoelectronic fields. Laser displays exhibit outstanding advantages in next-generation display technologies owing to their ultimate visual experience, but this remains a great challenge. Here, we develop a novel OLED based organic single crystals. By strongly coupling the organic exciton state to an optical microcavity, we obtain polariton electroluminescent (EL) emission from the polariton OLEDs (OPLEDs) with high luminance, narrow-band emission, high color purity, high polarization as well as excellent optically pumped polariton laser. Further, we evaluate the potential for electrically pumped polariton laser through theoretical analysis and provide possible solutions. This work provides a powerful strategy with a material-device combination that paves the way for electrically driven organic single-crystal-based polariton luminescent devices and possibly lasers.
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PURPOSE: To investigate the incidence, risk factors, and clinical impact of persistent coronal imbalance (PCI) in Lenke5C adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF). METHODS: We analyzed the medical records of 112 Lenke5C AIS patients. They were grouped into PCI (+) group and PCI (-) group according to the occurrence of PCI at 2 years after surgery. Coronal and sagittal parameters were measured and compared between both groups preoperatively, immediately postoperatively, and 2 years postoperatively. Scoliosis Research Societyâ22 (SRSâ22) score was used to evaluate clinical outcomes. RESULTS: Of the 112 patients, 12 had coronal imbalance persisting 2 years after surgery. Logistic regression analysis indicated risk factors including older age [odds ratio(OR)= 1.841, 95% confidence interval (CI) 1.147-2.132, P = 0.001], lower preoperative flexibility main thoracic (MT) curve (OR = 1.308,95% CI: 1.041-2.015, P = 0.016), greater preoperative apical vertebral translation (AVT) of the thoracolumbar/lumbar (TL/L) curve (AVT-TL/L) (OR= 2.291, 95%CI: 1.120-4.719, P = 0.001), larger preoperative lowest instrumented vertebra tilt (LIV lilt) (OR = 2.141, 95% CI: 1.491-3.651, P = 0.011), postoperative immediate coronal imbalance (OR = 5.512, 95% CI: 4.531-6.891, P = 0.001). The satisfaction and total score of SRS-22 scale in PCI (+) group were lower than those in PCI (-) group at 2 years after surgery (P < 0.05). CONCLUSIONS: We found a 10.7% incidence of PCI in patients with Lenke5C AIS undergoing PSF. PCI adversely affects clinical outcomes. Risk factors of PCI included older age, reduced preoperative MT curve flexibility, increased preoperative AVT in the TL/L curve, greater preoperative LIV tilt, and immediate postoperative coronal imbalance.
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The intricate nature of pain classification and mechanism constantly affects the recovery of diseases and the well-being of patients. Key medical challenges persist in devising effective pain management strategies. Therefore, a comprehensive review of relevant methods and research advancements in pain management is conducted. This overview covers the main categorization of pain and its developmental mechanism, followed by a review of pertinent research and techniques for managing pain. These techniques include commonly prescribed medications, invasive procedures, and noninvasive physical therapy methods used in rehabilitation medicine. Additionally, for the first time, a systematic summary of the utilization of responsive biomaterials in pain management is provided, encompassing their response to physical stimuli such as ultrasound, magnetic fields, electric fields, light, and temperature, as well as changes in the physiological environment like reactive oxygen species (ROS) and pH. Even though the application of responsive biomaterials in pain management remains limited and at a fundamental level, recent years have seen the examination and debate of relevant research findings. These profound discussions aim to provide trends and directions for future research in pain management.
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A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)-1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes.
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Asma , Proteínas de Ciclo Celular , Células Epiteliais , Ferroptose , Proteínas de Membrana Transportadoras , Mitocôndrias , Mitofagia , Fenótipo , Fator de Transcrição TFIIIA , Humanos , Mitocôndrias/metabolismo , Asma/metabolismo , Asma/patologia , Células Epiteliais/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Fator de Transcrição TFIIIA/metabolismo , Fator de Transcrição TFIIIA/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Masculino , Proteínas Quinases/metabolismo , Feminino , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Animais , Peroxidação de Lipídeos , Camundongos , Pessoa de Meia-IdadeRESUMO
The impacts of straw removal on rice Cd absorption, behaviour of Cd and microbial community in rhizosphere soil were investigated in paddy fields over two consecutive seasons. The results of the experiments in two fields revealed that straw removal promoted the transformation of soil Cd from acid-extractable and oxidisable fraction to residual fraction and reduced soil DTPA-Cd content with the reduction in DOC and Cd ions in soil porewater, thereby decreasing Cd content in rice. Specifically, the Cd content in brown rice was below 0.2 mg·kg-1 when all rice straw and roots were removed in the slightly Cd-contaminated soils. The α-diversity of soil microbial communities was less influenced by continuous straw removal, ß-diversity was altered and the relative abundances of Anaeromyxobacter, Methylocystis and Mycobacterium microbes were increased. Redundancy analysis and network analysis exhibited that soil pH predominantly influenced the microbial community. Path analysis revealed that the Cd content in brown rice could be directly influenced by the soil Total-Cd and DTPA-Cd, as well as soil pH and OM. Straw removal, including roots removal, is an economical and effective technique to reduce Cd accumulation in rice plants.
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Cádmio , Oryza , Microbiologia do Solo , Poluentes do Solo , Oryza/metabolismo , Cádmio/metabolismo , Cádmio/análise , Poluentes do Solo/metabolismo , Solo/química , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Rizosfera , Agricultura , Bactérias/metabolismo , Concentração de Íons de Hidrogênio , MicrobiotaRESUMO
Designing the polarization degree of freedom of light is crucial in many fields and has widespread application in, for example, all-optical circuits. In this work, we find that in an organic microcavity filled with anisotropic single crystals the cavity modes can be modulated to be elliptically polarized, i.e., partially circularly polarized and partially linearly polarized. The circular polarization component originates from the Rashba-Dresselhaus spin splitting, while the linear polarization component is due to the dislocation of linearly polarized modes. The dislocation of the linear polarizations is ascribed to the orientation of individual molecules and the molecular packing arrangement; hence, the linear polarizations can be controlled by properly structuring the molecular distributions. Our results pave the way for enriching and engineering the polarization properties of individual optical cavity modes in organic microstructures, which may favor the development of polarized lasers with various polarizations.
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Endotracheal tube dislodgement is a common patient safety incident in clinical settings. Current clinical practices, primarily relying on bedside visual inspections and equipment checks, often fail to detect endotracheal tube displacement or dislodgement promptly. This study involved the development of a deep learning, artificial intelligence (AI)-based system for monitoring tube displacement. We also propose a randomized crossover experiment to evaluate the effectiveness of this AI-based monitoring system compared to conventional methods. The assessment will focus on immediacy in detecting and handling of tube anomalies, the completeness and accuracy of shift transitions, and the degree of innovation diffusion. The findings from this research are expected to offer valuable insights into the development and integration of AI in enhancing care provision and facilitating innovation diffusion in medical and nursing research.
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Inteligência Artificial , Intubação Intratraqueal , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Humanos , Estudos Cross-Over , Monitorização Fisiológica/instrumentação , Aprendizado ProfundoRESUMO
In recent years, bladder carcinoma (BC) has shown an increasing incidence, with poor patient outcomes. In clinical practice, BC is still mainly treated by surgery combined with chemoradiotherapy. However, as chemotherapy resistance of tumor cells becomes more and more obvious, it is urgent to find more effective BC treatment regimes. With the increasing application and growing attention paid to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in various neoplastic diseases, EGFR-TKIs have been considered as a new treatment direction in the future. In this study, the research team used AG1478, an EGFR-TKI, to intervene with the BC cell line T24. It was found that the cell activity was statistically decreased, the apoptosis was enhanced, and the cells were dominantly arrested in the G0/G1 phase, confirming the future therapeutic potential of EGFR-TKIs in BC. Besides, the research team further observed that AG1478 also promoted pyroptosis in T24 cells, and its mechanism is related to the induction of mitochondrial oxidative stress damage. The findings lay a more reliable foundation for the future application of EGFR-TKIs in BC.
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Apoptose , Pontos de Checagem do Ciclo Celular , Receptores ErbB , Mitocôndrias , Inibidores de Proteínas Quinases , Quinazolinas , Tirfostinas , Neoplasias da Bexiga Urinária , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Tirfostinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Lung injury in sepsis is caused by an excessive inflammatory response caused by the entry of pathogenic microorganisms into the body. It is also accompanied by the production of large amounts of ROS. Ferroptosis and mitochondrial dysfunction have also been shown to be related to sepsis. Finding suitable sepsis therapeutic targets is crucial for sepsis research. BTB domain-containing protein 7 (KBTBD7) is involved in regulating inflammatory responses, but its role and mechanism in the treatment of septic lung injury are still unclear. In this study, we evaluated the role and related mechanisms of KBTBD7 in septic lung injury. In in vitro studies, we established an in vitro model by inducing human alveolar epithelial cells with lipopolysaccharide (LPS) and found that KBTBD7 was highly expressed in the in vitro model. KBTBD7 knockdown could reduce the inflammatory response by inhibiting the secretion of pro-inflammatory factors and inhibit the production of ROS, ferroptosis and mitochondrial dysfunction. Mechanistic studies show that KBTBD7 interacts with FOXA1, promotes FOXA1 expression, and indirectly inhibits SLC7A11 transcription. In vivo studies have shown that knocking down KBTBD7 improves lung tissue damage in septic lung injury mice, inhibits inflammatory factors, ROS production and ferroptosis. Taken together, knockdown of KBTBD7 shows an alleviating effect on septic lung injury in vitro and in vivo, providing a potential therapeutic target for the treatment of septic lung injury.
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Sistema y+ de Transporte de Aminoácidos , Ferroptose , Lesão Pulmonar , Mitocôndrias , Sepse , Animais , Humanos , Masculino , Camundongos , Células Epiteliais Alveolares/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Lipopolissacarídeos , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental condition distinguished by unconventional neural activities. Early intervention is key to managing the progress of ASD, and current research primarily focuses on the use of structural magnetic resonance imaging (sMRI) or resting-state functional magnetic resonance imaging (rs-fMRI) for diagnosis. Moreover, the use of autoencoders for disease classification has not been sufficiently explored. In this study, we introduce a new framework based on autoencoder, the Deep Canonical Correlation Fusion algorithm based on Denoising Autoencoder (DCCF-DAE), which proves to be effective in handling high-dimensional data. This framework involves efficient feature extraction from different types of data with an advanced autoencoder, followed by the fusion of these features through the DCCF model. Then we utilize the fused features for disease classification. DCCF integrates functional and structural data to help accurately diagnose ASD and identify critical Regions of Interest (ROIs) in disease mechanisms. We compare the proposed framework with other methods by the Autism Brain Imaging Data Exchange (ABIDE) database and the results demonstrate its outstanding performance in ASD diagnosis. The superiority of DCCF-DAE highlights its potential as a crucial tool for early ASD diagnosis and monitoring.
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Algoritmos , Transtorno do Espectro Autista , Encéfalo , Imageamento por Ressonância Magnética , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/diagnóstico , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodosRESUMO
IL-6 signaling plays a crucial role in the survival and metastasis of skin cancer. NEDD4L acts as a suppressor of IL-6 signaling by targeting GP130 degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma. Skin tumors were induced in wild-type and Nedd4l-knockout mice, and activation of the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cutaneous squamous cell carcinoma tissues from patients. Nedd4l deficiency significantly promoted 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.
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Autism spectrum disorder (ASD) is a complex, severe disorder related to brain development. It impairs patient language communication and social behaviors. In recent years, ASD researches have focused on a single-modal neuroimaging data, neglecting the complementarity between multi-modal data. This omission may lead to poor classification. Therefore, it is important to study multi-modal data of ASD for revealing its pathogenesis. Furthermore, recurrent neural network (RNN) and gated recurrent unit (GRU) are effective for sequence data processing. In this paper, we introduce a novel framework for a Multi-Kernel Learning Fusion algorithm based on RNN and GRU (MKLF-RAG). The framework utilizes RNN and GRU to provide feature selection for data of different modalities. Then these features are fused by MKLF algorithm to detect the pathological mechanisms of ASD and extract the most relevant the Regions of Interest (ROIs) for the disease. The MKLF-RAG proposed in this paper has been tested in a variety of experiments with the Autism Brain Imaging Data Exchange (ABIDE) database. Experimental findings indicate that our framework notably enhances the classification accuracy for ASD. Compared with other methods, MKLF-RAG demonstrates superior efficacy across multiple evaluation metrics and could provide valuable insights into the early diagnosis of ASD.
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Sweet sorghum has a large biomass and strong cadmium (Cd) absorption capacity, which has the potential for phytoremediation of Cd-contaminated soil. In order to study the Cd phytoremediation effect of sweet sorghum assisted with citric acid on the typical parent materials in southern China, a field experiment was carried out in two typical parent material farmland areas (neutral purple mud field and jute sand mud field) with Cd pollution in Hunan Province. The results showed that:â Citric acid had no inhibitory effect on the growth of sweet sorghum. After the application of citric acid, the aboveground biomass of sweet sorghum at the maturity stage increased by 10.1%-24.7%. â¡ Both sweet sorghum planting and citric acid application reduced the soil pH value, and the application of citric acid further reduced the soil pH value at each growth stage of sweet sorghum; this decrease was greater in the neutral purple mud field, which decreased by 0.24-0.72 units. ⢠Both sweet sorghum planting and citric acid application reduced the total amount of soil Cd, and the decreases in the neutral purple mud field and jute sand mud field were 23.8%-52.2% and 17.1%-31.8%, respectively. The acid-extractable percentage of soil Cd in both places increased by 38.6%-147.7% and 4.8%-22.7%, respectively. ⣠The application of citric acid could significantly increase the Cd content in various tissues of sweet sorghum. The Cd content in the aboveground part of the plant in the neutral purple mud field was higher than that in the jute sand mud field, and the Cd content in stems and leaves was 0.25-1.90 mg·kg-1 and 0.21-0.64 mg·kg-1, respectively. ⤠After applying citric acid, the Cd extraction amount of sweet sorghum in neutral purple mud soil in the mature stage reached 47.56 g·hm-2. In summary, citric acid could enhance the efficiency of sweet sorghum in the phytoremediation of Cd-contaminated soil, and the effect was better in neutral purple mud fields. This technology has the potential for remediation coupled with agro-production for heavy metal-contaminated farmland.
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Poluentes do Solo , Sorghum , Cádmio/análise , Biodegradação Ambiental , Solo , Areia , Ácido Cítrico , Poluentes do Solo/análise , China , Grão Comestível/químicaRESUMO
A rice pot experiment was conducted to identify the effect of silica fertilizer prepared from husk ash on the soil bioavailability of cadmium (Cd) and arsenic (As), enzyme activities, microbial community structure, and heavy metal content in brown rice at different growth stages. The results showed that the application of 0.1%-1.0% silica fertilizer-husk ash increased the pH value of soil by 0.04-0.24 units and the content of soil available silicon by 44.2%-97.5%. It also decreased the content of available Cd and available As by 16.2%-21.4% and 16.0%-24.9%, respectively. With the increase in application amount, the soil enzyme activities increased at all growth stages, and the sucrase activity and the dehydrogenase activity significantly increased by 6.3%-145.7% and 6.7%-224.1%, respectively. The analysis of the soil microbial community composition structure at mature stages showed that the application of silica fertilizer-husk ash had no effect on microbial α-diversity, but it had a significant effect on microbial ß-diversity and then promoted microbial growth and maintained the stability of the community structure. With the increase in application amount, the contents of Cd in brown rice decreased by 29.3%-89.7%, and the contents of total As and inorganic As in brown rice decreased by 7.8%-42.3% and 17.2%-44.5%, respectively. Under the application of 0.5% and 1.0% silica fertilizer-husk ash, the Cd contents in brown rice were lower than 0.2 mg·kg-1, and the inorganic As contents in brown rice were lower than 0.35 mg·kg-1. In conclusion, the silica fertilizer-husk ash can improve soil quality and reduce the contents of Cd and As in brown rice, and it is eco-friendly and can be used to remedy the paddy soil contaminated with Cd and As.
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Arsênio , Oryza , Poluentes do Solo , Cádmio/análise , Arsênio/análise , Dióxido de Silício , Solo/química , Oryza/química , Fertilizantes/análise , Poluentes do Solo/análiseRESUMO
In this studyï¼ a field experiment was conducted to examine the effects of the application of irrigation water containing Zn at the key growth period ï¼booting stage and filling stageï¼ on exchangeable Cd content in the soilï¼ Cd concentration in pore waterï¼ and Cd uptake and transport in rice in a Cd-contaminated paddy field in Liuyang Cityï¼ Hunan Province. The results indicated thatï¼ â the application of irrigation water containing Zn during the key growth period could inhibit the releasing process of exchangeable Cd from the soil into pore water. Compared with that in the controlï¼ the content of exchangeable Cd in soil was slightly changedï¼ but the concentration of Cd in soil pore water at the mature stage was significantly reduced by 16.7%-57.6%. â¡ The application of irrigation water containing Zn at the key growth period could significantly reduce the Cd content in various parts of rice. Cd contents in rootï¼ stemï¼ and brown rice with the application of irrigation water containing 20 mg·L-1 Zn before the booting and the filling stage ï¼BF1ï¼ were significantly decreased by 56.0%ï¼ 83.8%ï¼ and 85.2%ï¼ respectively. ⢠Compared with the application of 100 mg·L-1 irrigation water containing Znï¼ the application of 20 mg·L-1 irrigation water containing Zn significantly reduced the uptake and transport of Cd in riceï¼ and the translocation factor ï¼TFï¼ of Cd from rice roots to stems was also significantly reduced by 12.5%-56.3%ï¼ with the B1 and BF1 treatments reaching significant levels. These results suggested that the application of irrigation water containing Zn could significantly reduce the uptake and accumulation of Cd in riceï¼ and the application of 20 mg·L-1 irrigation water containing Zn before the booting and filling stage could effectively realize the safe production of Cd-contaminated paddy fields.
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Oryza , Poluentes do Solo , Cádmio/análise , Poluentes do Solo/análise , Solo , Água , ZincoRESUMO
BACKGROUND: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. METHODS: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received a booster with the adapted Comirnaty Original/Omicron BA.4-5 vaccine 8.3 months after the fourth vaccination and/or experienced a breakthrough infection. Two months before and four weeks after the fifth vaccination, the live-virus neutralization capacities of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were determined, as well as neutralizing and quantitative anti-SARS-CoV-2 spike-specific IgG antibodies. RESULTS: Four weeks after the fifth vaccination with the adapted vaccine, significantly increased neutralizing antibodies and the neutralization of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were observed. The increase was significantly higher than after the fourth vaccination for variants BQ.1.1 and BA.5. Of all analyzed variants, BA.5 was neutralized best after the fifth vaccination. We did not see a difference in humoral immunity between the group with an infection and the group with a vaccination as a fifth spike exposure. Fivefold-vaccinated patients with a breakthrough infection showed a significantly higher neutralization capacity of XBB.1.5. CONCLUSION: A fifth SARS-CoV-2 vaccination with the adapted vaccine improves both wild-type specific antibody titers and the neutralizing capacity of the current Omicron variants BA.5, BQ.1.1, and XBB.1.5 in hemodialysis patients. Additional booster vaccinations with adapted vaccines will likely improve immunity towards current and original SARS-CoV-2 variants and are, therefore, recommended in hemodialysis patients. Further longitudinal studies must show the extent to which this booster vaccination avoids a breakthrough infection.
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Cervical cytology image classification is of great significance to the cervical cancer diagnosis and prognosis. Recently, convolutional neural network (CNN) and visual transformer have been adopted as two branches to learn the features for image classification by simply adding local and global features. However, such the simple addition may not be effective to integrate these features. In this study, we explore the synergy of local and global features for cytology images for classification tasks. Specifically, we design a Deep Integrated Feature Fusion (DIFF) block to synergize local and global features of cytology images from a CNN branch and a transformer branch. Our proposed method is evaluated on three cervical cell image datasets (SIPaKMeD, CRIC, Herlev) and another large blood cell dataset BCCD for several multi-class and binary classification tasks. Experimental results demonstrate the effectiveness of the proposed method in cervical cell classification, which could assist medical specialists to better diagnose cervical cancer.
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Neoplasias do Colo do Útero , Feminino , Humanos , Aprendizagem , Redes Neurais de Computação , Processamento de Imagem Assistida por ComputadorRESUMO
Renal cell carcinoma (RCC) arises from the tubular epithelial cells of the nephron. It has the highest mortality rate among urological cancers. There are no effective therapeutic approaches and no non-invasive biomarkers for diagnosis and follow-up. Thus, suitable novel biomarkers and therapeutic targets are essential for improving RCC diagnosis/prognosis and treatment. Circulating exosomes such as exosomal microRNAs (Exo-miRs) provide non-invasive prognostic/diagnostic biomarkers and valuable therapeutic targets, as they can be easily isolated and quantified and show high sensitivity and specificity. Exosomes secreted by an RCC can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a ''signature'' or ''fingerprint'' of the donor cell. It has been shown that the transportation of renal-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in RCC. The present review highlights the studies reporting tumor microenvironment-derived Exo-miRs with therapeutic potential as well as circulating Exo-miRs as potential diagnostic/prognostic biomarkers in patients with RCC.
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Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Humanos , MicroRNAs/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Prognóstico , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Biomarcadores , Biomarcadores Tumorais/genética , Microambiente TumoralRESUMO
Objective: The PRAS40 is an essential inhibitory subunit of the mTORC1 complex, which regulates autophagy. It has been suggested that Erxian Decoction (EXD) could treat spinal cord injury (SCI) via the autophagy pathway. However, the mechanism of whether EXD acts through PRAS40 remains unclear. Methods: With the help of immobilized PRAS40, isothermal titration calorimetry (ITC) and molecular docking, the bioactive metabolites in the EXD were screened. To establish in vitro SCI models, PC12 cells were exposed to hydrogen peroxide (H2O2) and then treated with the identified EXD substances. Furthermore, Western blot assay was carried out to identify potential molecular mechanisms involved. For assessing the effect of metabolites in vivo, the SCI model rats were first pretreated with or without the metabolite and then subjected to the immunohistochemistry (IHC) staining, Basso, Beattie & Bresnahan (BBB) locomotor rating scale, and H&E staining. Results: The immobilized PRAS40 isolated indole, 4-nitrophenol, terephthalic acid, palmatine, sinapinaldehyde, and 3-chloroaniline as the potential ligands binding to PRAS40. Furthermore, the association constants of palmatine and indole as 2.84 × 106 M-1 and 3.82 × 105 M-1 were elucidated via ITC due to the drug-like properties of these two metabolites. Molecular docking results also further demonstrated the mechanism of palmatine binding to PRAS40. Western blot analysis of PC12 cells demonstrated that palmatine inhibited the expression of p-mTOR by binding to PRAS40, activating the autophagic flux by markedly increasing LC3. The injection of palmatine (10µM and 20 µM) indicated notably increased BBB scores in the SCI rat model. Additionally, a dose-dependent increase in LC3 was observed by IHC staining. Conclusion: This research proved that EXD comprises PRAS40 antagonists, and the identified metabolite, palmatine, could potentially treat SCI by activating the autophagic flux.