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The enhanced Coulomb interaction in two-dimensional semiconductors leads to tightly bound electron-hole pairs known as excitons. The large binding energy of excitons enables the formation of Rydberg excitons with high principal quantum numbers (n), analogous to Rydberg atoms. Rydberg excitons possess strong interactions among themselves as well as sensitive responses to external stimuli. Here, we probe Rydberg exciton resonances through photocurrent spectroscopy in a monolayer WSe2 p-n junction formed by a split-gate geometry. We show that an external in-plane electric field not only induces a large Stark shift of Rydberg excitons up to quantum principal number 3 but also mixes different orbitals and brightens otherwise dark states such as 3p and 3d. Our study provides an exciting platform for engineering Rydberg excitons for new quantum states and quantum sensing.
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Fluorescence in situ hybridization (FISH) is a widely used technique for detecting intracellular nucleic acids. However, its effectiveness in detecting low-copy nucleic acids is limited due to its low fluorescence intensity and background autofluorescence. To address these challenges, we present here an approach of lanthanide-complex-enhanced bioorthogonal-branched DNA amplification (LEBODA) with high sensitivity for in situ nuclear acid detection in single cells. The approach capitalizes on two levels of signal amplification. First, it utilizes click chemistry to directly link a substantial number of bridge probes to target-recognizing probes, providing an initial boost in signal intensity. Second, it incorporates high-density lanthanide complexes into each bridge probe, enabling secondary amplifications. Compared to the traditional "double Z" probes used in the RNAscope method, LEBODA exhibits 4 times the single enhancement for RNA detection signal with the click chemistry approach. Using SARS-CoV-2 pseudovirus-infected HeLa cells, we demonstrate the superiority in the detection of viral-infected cells in rare populations as low as 20% infectious rate. More encouragingly, the LEBODA approach can be adapted for DNA-FISH and single-molecule RNA-FISH, as well as other hybridization-based signal amplification methods. This adaptability broadens the potential applications of LEBODA in the sensitive detection of biomolecules, indicating promising prospects for future research and practical use.
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Elementos da Série dos Lantanídeos , Humanos , Hibridização in Situ Fluorescente/métodos , Células HeLa , RNA , DNA/genética , Sondas de DNA/genéticaRESUMO
Traditional single-molecule fluorescence in situ hybridization (smFISH) methods for RNA detection often face sensitivity challenges due to the low fluorescence intensity of the probe. Also, short-lived autofluorescence complicates obtaining clear signals from tissue sections. In response, we have developed an smFISH probe using highly grafted lanthanide complexes to address both concentration quenching and autofluorescence background. Our approach involves an oligo PCR incorporating azide-dUTP, enabling conjugation with lanthanide complexes. This method has proven to be stable, convenient, and cost-effective. Notably, for the mRNA detection in SKBR3 cells, the lanthanide probe group exhibited 2.5 times higher luminescence intensity and detected 3 times more signal points in cells compared with the Cy3 group. Furthermore, we successfully applied the probe to image HER2 mRNA molecules in breast cancer FFPE tissue sections, achieving a 2.7-fold improvement in sensitivity compared to Cy3-based probes. These results emphasize the potential of time-resolved smFISH as a highly sensitive method for nucleic acid detection, free of background fluorescence interference.
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Elementos da Série dos Lantanídeos , Hibridização in Situ Fluorescente/métodos , RNA/análise , RNA Mensageiro/genética , Diagnóstico por ImagemRESUMO
Increasing evidence suggests that key cancer-causing driver genes continue to exert a sustained influence on the tumor microenvironment (TME), highlighting the importance of immunotherapeutic targeting of gene mutations in governing tumor progression. TP53 is a prominent tumor suppressor that encodes the p53 protein, which controls the initiation and progression of different tumor types. Wild-type p53 maintains cell homeostasis and genomic instability through complex pathways, and mutant p53 (Mut p53) promotes tumor occurrence and development by regulating the TME. To date, it has been wildly considered that TP53 is able to mediate tumor immune escape. Herein, we summarized the relationship between TP53 gene and tumors, discussed the mechanism of Mut p53 mediated tumor immune escape, and summarized the progress of applying p53 protein in immunotherapy. This study will provide a basic basis for further exploration of therapeutic strategies targeting p53 protein.
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Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Genes p53 , Neoplasias/genética , Cognição , Instabilidade Genômica , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Congenital dislocation of the knee is characterised by excessive knee extension or dislocation and anterior subluxation of the proximal tibia, and this disease can occur independently or coexist with different systemic syndromes. Nevertheless, significant controversy surrounds treating this disease when combined with hip dislocation. This paper presents a case of a 4-month-old patient diagnosed with bilateral hip dislocation combined with this disease. The study discusses the pathophysiology, diagnosis, and treatment methods and reviews relevant literature. CASE PRESENTATION: We reported a case of a 4-month-old female infant with congenital dislocation of the right knee joint, which presented as flexion deformity since birth. Due to limitations in local medical conditions, she did not receive proper and effective diagnosis and treatment. Although the flexion deformity of her right knee joint partially improved without treatment, it did not fully recover to normal. When she was 4 months old, she came to our hospital for consultation, and we found that she also had congenital dislocation of both hip joints and atrial septal defect. We performed staged treatment for her, with the first stage involving surgical intervention and plaster orthosis for her congenital dislocation of the right knee joint, and the second stage involving closed reduction and plaster fixation orthosis for her congenital hip joint dislocation. Currently, the overall treatment outcome is satisfactory, and she is still under follow-up observation. CONCLUSIONS: Early initiation of treatment is generally advised, as nonsurgical methods prove satisfactory for mild cases. However, surgical intervention should be considered in cases with severe stiffness, unresponsive outcomes to conservative treatment, persistent deformities, or diagnoses and treatments occurring beyond the first month after birth.
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Luxação Congênita de Quadril , Luxação do Joelho , Humanos , Feminino , Luxação do Joelho/complicações , Luxação do Joelho/congênito , Luxação do Joelho/terapia , Luxação do Joelho/diagnóstico por imagem , Luxação do Joelho/cirurgia , Luxação do Joelho/diagnóstico , Luxação Congênita de Quadril/complicações , Luxação Congênita de Quadril/terapia , Luxação Congênita de Quadril/diagnóstico , Lactente , Resultado do Tratamento , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Moldes CirúrgicosRESUMO
AIMS: To map the existing literature describing medical device-related pressure injuries in patients during surgery, including investigation of the incidence, types of medical devices, risk factors and strategies for preventing medical device-related pressure injuries. DESIGN: A scoping review. DATA SOURCES: In April 2023, three databases were searched. Studies about adult patients undergoing surgery, from 2014 onwards, in English and Chinese were included. Data were extracted about study characteristics and data related to research questions. The Patterns, Advances, Gaps, Evidence for practice and Research recommendations framework were used to synthesize findings. RESULTS: Two different types of evidence were included in this review; 14 research studies and two quality improvement studies. The incidence of medical device-related pressure injuries in the operating room was 0.56%-24.5% and respiratory devices were the most common medical devices investigated. Length of surgery, age and BMI were risk factors for medical device-related pressure injuries in a few studies. The application of a prophylactic dressing and dressing maintenance was the most common prevention strategy. CONCLUSION: Ongoing research is needed to confirm the incidence of, and risk factors for, medical device-related pressure injuries in the operating room. Additionally, more high-quality evidence is needed to underpin current prevention strategies. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Operating room nurses need to be aware of the risks of medical device-related pressure injuries and assess and plan prevention strategies accordingly. Once more high-quality evidence is available, operating room nurses could implement prevention strategies like prophylactic dressings. REPORTING METHOD: Scoping Reviews (PRISMA-ScR) checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Yield improvement has long been an important task for soybean breeding in the world in order to meet the increasing demand for food and animal feed. miR396 genes have been shown to negatively regulate grain size in rice, but whether miR396 family members may function in a similar manner in soybean is unknown. Here, we generated eight soybean mutants harboring different combinations of homozygous mutations in the six soybean miR396 genes through genome editing with clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas)12SF01 in the elite soybean cultivar Zhonghuang 302 (ZH302). Four triple mutants (mir396aci, mir396acd, mir396adf, and mir396cdf), two quadruple mutants (mir396abcd and mir396acfi), and two quintuple mutants (mir396abcdf and mir396bcdfi) were characterized. We found that plants of all the mir396 mutants produced larger seeds compared to ZH302 plants. Field tests showed that mir396adf and mir396cdf plants have significantly increased yield in growth zones with relatively high latitude which are suited for ZH302 and moderately increased yield in lower latitude. In contrast, mir396abcdf and mir396bcdfi plants have increased plant height and decreased yield in growth zones with relatively high latitude due to lodging issues, but they are suited for low latitude growth zones with increased yield without lodging problems. Taken together, our study demonstrated that loss-of-function of miR396 genes leads to significantly enlarged seed size and increased yield in soybean, providing valuable germplasms for breeding high-yield soybean.
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Glycine max , MicroRNAs , Sementes , Glycine max/genética , Glycine max/crescimento & desenvolvimento , MicroRNAs/genética , MicroRNAs/metabolismo , Sementes/genética , Mutação/genética , Genes de Plantas , Edição de Genes , Técnicas de Inativação de GenesRESUMO
BACKGROUND: Type 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center. METHODS: The data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011-2022 were retrospectively analyzed. RESULTS: The average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were < 1 cm, 69.4% were NET G1, and 2.2% were stage III-IV. A total of 76.9% of the patients had received endoscopic management, 60.7% had received traditional Chinese medicine treatment, 10.5% received somatostatin analogues treatment, and 6.6% underwent surgical resection. Seventy patients (41.2%) experienced the first recurrence after a median follow-up of 31 months (range: 2-122 months), and the median recurrence-free time was 43 months. The 1-, 2-, and 3-year cumulative recurrence-free survival rates were 71.8%, 56.8%, and 50.3%, respectively. During a median follow-up of 39 months (range: 2-132 months), one patient had bilateral pulmonary metastasis, and no disease-related deaths were observed. CONCLUSION: Type 1 gastric NETs have a high recurrence rate and a long disease course, underscoring the importance of long-term and comprehensive management.
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Tumores Neuroendócrinos , Neoplasias Gástricas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMO
We aimed to explore the therapeutic effects of endoscopically assisted surgical approaches for HICH. In this retrospective cohort study, we retrospectively analyzed the treatment status of 118 patients with HICH who underwent surgery for hematoma removal. Among them, 61 patients underwent endoscopically assisted hematoma removal surgery through the frontal lobe approach (frontal lobe group); 57 patients underwent endoscopic hematoma assisted via the temporal lobe approach (temporal lobe group). Treatment effects, cerebral hemodynamic status before and after treatment, postoperative prognosis at one month, and incidence of complications were compared between the 2 groups. We found that the total effective treatment rate in the frontal lobe group was higher than that in the temporal lobe group (Pâ <â .05). After surgery, the R during the contraction period of the common cerebral artery in both groups decreased compared to that before surgery, and the frontal lobe group was significantly lower than the temporal lobe group; the V and Q were higher than those before surgery, and the frontal lobe group was significantly higher than the temporal lobe group (Pâ <â .05). The prognosis of the frontal lobe group was better than that of the temporal lobe group (Pâ <â .05). Compared to the endoscopic-assisted temporal approach, the endoscopic-assisted frontal lobe approach for the treatment of HICH can improve cerebral hemodynamic status, enhance treatment efficacy, and improve prognosis.
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Hemorragia Intracraniana Hipertensiva , Humanos , Estudos Retrospectivos , Hemorragia Intracraniana Hipertensiva/cirurgia , Endoscopia/efeitos adversos , Craniotomia , Resultado do Tratamento , Hematoma/etiologiaRESUMO
Deep convolution neural networks have been widely used in medical image analysis, such as lesion identification in whole-slide images, cancer detection, and cell segmentation, etc. However, it is often inevitable that researchers try their best to refine annotations so as to enhance the model performance, especially for cell segmentation task. Weakly supervised learning can greatly reduce the workload of annotations, while there is still a huge performance gap between the weakly and fully supervised learning approaches. In this work, we propose a weakly-supervised cell segmentation method, namely Multi-Task Cell Segmentation Network (MTCSNet), for multi-modal medical images, including pathological, brightfield, fluorescent, phase-contrast and differential interference contrast images. MTCSNet is learnt in a single-stage training manner, where only two annotated points for each cell provide supervision information, and the first one is the centroid, the second one is its boundary. Additionally, five auxiliary tasks are elaborately designed to train the network, including two pixel-level classifications, a pixel-level regression, a local temperature scaling and an instance-level distance regression task, which is proposed to regress the distances between the cell centroid and its boundaries in eight orientations. The experimental results indicate that our method outperforms all state-of-the-art weakly-supervised cell segmentation approaches on public multi-modal medical image datasets. The promising performance also shows that a single-stage learning with two-point labeling approach are sufficient for cell segmentation, instead of fine contour delineation. The codes are available at: https://github.com/binging512/MTCSNet.
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B7-H3 is a common oncogene found in various cancer types. However, the molecular mechanisms underlying abnormal B7-H3 expression and colorectal cancer (CRC) progression need to be extensively explored. B7-H3 was upregulated in human CRC tissues and its abnormal expression was correlated with a poor prognosis in CRC patients. Notably, gain- and loss-of-function experiments revealed that B7-H3 knockdown substantially inhibited cell proliferation, migration, and invasion in vitro, whereas exogenous B7-H3 expression yielded contrasting results. In addition, silencing of B7-H3 inhibited tumor growth in a xenograft mouse model. Mechanistically, our study demonstrated that the N6-methyladenosine (m6A) binding protein YTHDF1 augmented B7-H3 expression in an m6A-dependent manner. Furthermore, rescue experiments demonstrated that reintroduction of B7-H3 considerably abolished the inhibitory effects on cell proliferation and invasion induced by silencing YTHDF1. Our results suggest that the YTHDF1-m6A-B7-H3 axis is crucial for CRC development and progression and may represent a potential therapeutic target for CRC treatment.
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Mitosis is a crucial biological process where a parental cell undergoes precisely controlled functional phases and divides into two daughter cells. Some drugs can inhibit cell mitosis, for instance, the anti-cancer drugs interacting with the tumor cell proliferation and leading to mitosis arrest at a specific phase or cell death eventually. Combining machine learning with microfluidic impedance flow cytometry (IFC) offers a concise way for label-free and high-throughput classification of drug-treated cells at single-cell level. IFC-based single-cell analysis generates a large amount of data related to the cell electrophysiology parameters, and machine learning helps establish correlations between these data and specific cell states. This work demonstrates the application of machine learning for cell state classification, including the binary differentiations between the G1/S and apoptosis states and between the G2/M and apoptosis states, as well as the classification of three subpopulations comprising a subgroup insensitive to the drug beyond the two drug-induced states of G2/M arrest and apoptosis. The impedance amplitudes and phases used as input features for the model training were extracted from the IFC-measured datasets for the drug-treated tumor cells. The deep neural network (DNN) model was exploited here with the structure (e.g., hidden layer number and neuron number in each layer) optimized for each given cell type and drug. For the H1650 cells, we obtained an accuracy of 78.51% for classification between the G1/S and apoptosis states and 82.55% for the G2/M and apoptosis states. For HeLa cells, we achieved a high accuracy of 96.94% for classification between the G2/M and apoptosis states, both of which were induced by taxol treatment. Even higher accuracy approaching 100% was achieved for the vinblastine-treated HeLa cells for the differentiation between the viable and non-viable states, and between the G2/M and apoptosis states. We also demonstrate the capability of the DNN model for high-accuracy classification of the three subpopulations in a complete cell sample treated by taxol or vinblastine.
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Hematological indicators of chronic systemic inflammation are significant biomarkers for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). We performed a systematic review and meta-analysis to assess the impact of certain factors on the overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of patients with GEP-NENs. These factors include the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and C-reactive protein (CRP) levels. After searching the Medline, Embase, and Cochrane Library databases from January 1, 2000 to October 20, 2022 and the American Society of Clinical Oncology conference proceedings from January 1, 2017, hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted. Subgroup analyses were conducted to identify the origins of heterogeneity and examine the impact of factor grouping. The effects of the cut-off values and sample size were assessed by meta-regression. The results revealed that higher NLRs, PLRs, and CRP levels were associated with shorter OS (HR = 2.09, 95% CI = 1.55-2.8; HR = 1.79, 95% CI = 1.40-2.28; and HR = 2.88, 95% CI = 2.09-3.95, respectively; all p < 0.001). Higher NLRs and lower LMRs were associated with shorter DFS (HR = 3.34, 95% CI = 2.11-5.29 and HR = 2.71, 95% CI = 2.27-3.24, respectively; both p < 0.001). Higher PLRs and CRP levels were correlated with shorter PFS (HR = 3.48, 95% CI = 1.34-9.03, p = 0.01 and HR = 3.14, 95% CI = 1.63-6.08, p = 0.001). As demonstrated in the research, hematological indicators of systemic inflammation are promising biomarkers for GEP-NEN assessment.
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Linfócitos , Tumores Neuroendócrinos , Humanos , Prognóstico , Biomarcadores/metabolismo , Linfócitos/metabolismo , Inflamação/metabolismo , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/metabolismoRESUMO
AIMS: Sleep disturbance is a prevalent nonmotor symptom of Parkinson's disease (PD), however, assessing sleep conditions is always time-consuming and labor-intensive. In this study, we performed an automatic sleep-wake state classification and early diagnosis of PD by analyzing the electrocorticography (ECoG) and electromyogram (EMG) signals of both normal and PD rats. METHODS: The study utilized ECoG power, EMG amplitude, and corticomuscular coherence values extracted from normal and PD rats to construct sleep-wake scoring models based on the support vector machine algorithm. Subsequently, we incorporated feature values that could act as diagnostic markers for PD and then retrained the models, which could encompass the identification of vigilance states and the diagnosis of PD. RESULTS: Features extracted from occipital ECoG signals were more suitable for constructing sleep-wake scoring models than those from frontal ECoG (average Cohen's kappa: 0.73 vs. 0.71). Additionally, after retraining, the new models demonstrated increased sensitivity to PD and accurately determined the sleep-wake states of rats (average Cohen's kappa: 0.79). CONCLUSION: This study accomplished the precise detection of substantia nigra lesions and the monitoring of sleep-wake states. The integration of circadian rhythm monitoring and disease state assessment has the potential to improve the efficacy of therapeutic strategies considerably.
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Doença de Parkinson , Ratos , Animais , Doença de Parkinson/diagnóstico , Máquina de Vetores de Suporte , Eletroencefalografia , Sono , VigíliaRESUMO
The objective of this study was to evaluate the predictive value of the Geriatric Nutritional Risk Index (GNRI) combined with the Systemic Immunoinflammatory Index (SII) for the risk of major adverse cardiovascular events (MACE) following percutaneous coronary intervention in elderly patients with acute coronary syndrome (ACS). We retrospectively reviewed the medical records of 1202 elderly patients with acute coronary syndromes divided into MACE and non-MACE groups according to whether they had a MACE. The sensitivity analysis utilized advanced machine learning algorithms to preliminarily identify the critical role of GNRI versus SII in predicting MACE risk. We conducted a detailed analysis using a restricted cubic spline approach to investigate the nonlinear relationship between GNRI, SII, and MACE risk further. We constructed a clinical prediction model based on three key factors: GNRI, SII, and Age. To validate the accuracy and usefulness of this model, we compared it to the widely used GRACE score using subject work and recall curves. Additionally, we compared the predictive value of models and GRACE scores in assessing the risk of MACE using the Integrated Discriminant Improvement Index (IDI) and the Net Reclassification Index (NRI). This study included 827 patients. The GNRI scores were lower in the MACE group than in the non-MACE group, while the SII scores were higher in the MACE group (P < 0.001). The multifactorial analysis revealed a low GNRI (OR = 2.863, 95% CI: 2.026-4.047, P = 0.001), High SII (OR = 3.102, 95% CI: 2.213-4.348, P = 0.001). The area under the curve (AUC) for the predictive model was 0.778 (95% CI: 0.744-0.813, P = 0.001), while the AUC for the GRACE score was 0.744 (95% CI: 0.708-0.779, P = 0.001). NRI was calculated to be 0.5569, with NRI + at 0.1860 and NRI- at 0.3708. The IDI was found to be 0.0571, with a P-value of less than 0.001. These results suggest that the newly developed prediction model is more suitable for use with the population in this study than the GRACE score. The model constructed using GNRI and SII demonstrated good standardization and clinical impact, as evidenced by the standard, DCA, and clinical impact curves. The study shows that combining GNRI and SII can be a simple, cost-effective, and valuable way to predict the risk of MACE within one year in elderly acute coronary syndromes.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Idoso , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/etiologia , Prognóstico , Estudos Retrospectivos , Modelos Estatísticos , Intervenção Coronária Percutânea/efeitos adversos , Medição de RiscoRESUMO
Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing's syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients' circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.
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Síndrome de Cushing , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Estados Unidos , Humanos , Mitotano/uso terapêutico , Hidrocortisona , Síndrome de Cushing/tratamento farmacológico , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Hormônio AdrenocorticotrópicoRESUMO
Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.
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Glioblastoma , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Glioblastoma/genética , Glioblastoma/patologia , Camundongos Nus , Proliferação de Células , Linhagem Celular Tumoral , Transdução de Sinais , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
OBJECTIVE: Nuclei segmentation is a crucial pre-task for pathological microenvironment quantification. However, the acquisition of manually precise nuclei annotations for improving the performance of deep learning models is time-consuming and expensive. METHODS: In this paper, an efficient nuclear annotation tool called NuSEA is proposed to achieve accurate nucleus segmentation, where a simple but effective ellipse annotation is applied. Specifically, the core network U-Light of NuSEA is lightweight with only 0.86 M parameters, which is suitable for real-time nuclei segmentation. In addition, an Elliptical Field Loss and a Texture Loss are proposed to enhance the edge segmentation and constrain the smoothness simultaneously. RESULTS: Extensive experiments on three public datasets (MoNuSeg, CPM-17, and CoNSeP) demonstrate that NuSEA is superior to the state-of-the-art (SOTA) methods and better than existing algorithms based on point, rectangle, and text annotations. CONCLUSIONS: With the assistance of NuSEA, a new dataset called NuSEA-dataset v1.0, encompassing 118,857 annotated nuclei from the whole-slide images of 12 organs is released. The codes and the new dataset are publicly available at https://github.com/dreambamboo/NuSEA/. SIGNIFICANCE: NuSEA provides a rapid and effective annotation tool for nuclei in histopathological images, benefiting future explorations in deep learning algorithms.
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Here we presented an electrophysiological dataset collected from layer V of the primary motor cortex (M1) and the corresponding behavior dataset from normal and hemi-parkinson rats over 5 consecutive weeks. The electrophysiological dataset was constituted by the raw wideband signal, neuronal spikes, and local field potential (LFP) signal. The open-field test was done and recorded to evaluate the behavior variation of rats among the entire experimental cycle. We conducted technical validation of this dataset through sorting the spike data to form action potential waveforms and analyzing the spectral power of LFP data, then based on these findings a closed-loop DBS protocol was developed by the oscillation activity response of M1 LFP signal. Additionally, this protocol was applied to the hemi-parkinson rat for five consecutive days while simultaneously recording the electrophysiological data. This dataset is currently the only publicly available dataset that includes longitudinal closed-loop DBS recordings, which can be utilized to investigate variations of neuronal activity within the M1 following long-term closed-loop DBS, and explore additional reliable biomarkers.
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Estimulação Encefálica Profunda , Córtex Motor , Animais , Ratos , Córtex Motor/fisiologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Potenciais de Ação , Comportamento Animal , Fenômenos Eletrofisiológicos , Neurônios/fisiologiaRESUMO
BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.