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Patients with distant metastasis of head and neck squamous cell carcinoma (HNSCC) often have a poor prognosis. However, early diagnosis of distant metastasis is challenging in clinical practice, and distant metastasis is often only detected in the late stages of tumor metastasis through imaging techniques. In this study, we utilized data from HNSCC patients collected from the TCGA database. Patients were divided into distant metastasis and nonmetastasis groups based on the tumor-node-metastasis (TNM) stage. We analyzed the differentially expressed genes between the two groups (DM/non-M DEGs) and their associated lncRNAs and generated a predictive model based on 23 lncRNAs that were significantly associated with the occurrence of distant metastasis in HNSCC patients. On this basis, we built a nomogram to predict the distant metastasis of HNSCC patients. Moreover, through WGCNA and Cytoscape software analysis of DM/non-M DEGs, we identified the gene most closely related to HNSCC distant metastasis: EIF5A. Our findings were validated using GEO data; EIF5A expression was significantly increased in the tumor tissues of HNSCC patients with distant metastasis. We then predicted miRNAs that can directly bind to EIF5A via the TargetScan and miRWalk websites, intersected them with differentially expressed miRNAs in the two groups from the TCGA cohort, and identified the only overlapping miRNA, miR-424; we predicted the direct binding site of EIF5A and miR-424 via the miRWalk website. Immunohistochemistry further revealed high expression of EIF5A in the primary tumor tissue of HNSCC patients with distant metastasis. These results provide a new perspective for the early diagnosis of distant metastasis in HNSCC patients and the study of the mechanisms underlying HNSCC distant metastasis.
Sujet(s)
, Régulation de l'expression des gènes tumoraux , Tumeurs de la tête et du cou , Métastase tumorale , Nomogrammes , Facteurs initiation chaîne peptidique , Protéines de liaison à l'ARN , Carcinome épidermoïde de la tête et du cou , Femelle , Humains , Mâle , Adulte d'âge moyen , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Analyse de profil d'expression de gènes , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/anatomopathologie , microARN/génétique , microARN/métabolisme , Facteurs initiation chaîne peptidique/génétique , Facteurs initiation chaîne peptidique/métabolisme , Pronostic , ARN long non codant/génétique , Protéines de liaison à l'ARN/génétique , Protéines de liaison à l'ARN/métabolisme , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/anatomopathologieRÉSUMÉ
Underground fractured rock masses are susceptible to failure under the combined influence of true triaxial stresses and pore pressure, posing severe threats to personnel and production safety of underground engineering. To investigate the influence of intermediate principal stress (σ2) on the mechanical and water diffusion volume change (ΔV) characteristics during the failure process of cracked rocks under stable pore pressure, this study conducted true triaxial strength experiments on cracked sandstone with stable pore pressure. The results demonstrated that with the increase of σ2, crack initiation stress (σci), crack damage stress (σcd) and the peak stress (σ1,peak) of cracked sandstone initially increase and then decrease. Conversely, ΔV tends to decrease first and then increase with the increase of σ2. This inverse relationship indicates that under elevated σ2, the decreased strength of cracked rock could lead to an increase in ΔV, which may increase the probability of water inrush disasters. The findings of this study provide a theoretical reference for the stability of rock mass engineering and the prevention of water inrush disasters.
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Due to the harsh operating environment and ultralong operating hours of wireless sensor networks (WSNs), node failures are inevitable. Ensuring the reliability of the data collected by the WSN necessitates the utmost importance of diagnosing faults in nodes within the WSN. Typically, the initial step in the fault diagnosis of WSN nodes involves extracting numerical features from neighboring nodes. A solitary data feature is often assigned a high weight, resulting in the failure to effectively distinguish between all types of faults. Therefore, this study introduces an enhanced variant of the traditional belief rule base (BRB), called the belief rule base with adaptive attribute weights (BRB-AAW). First, the data features are extracted as input attributes for the model. Second, a fault diagnosis model for WSN nodes, incorporating BRB-AAW, is established by integrating parameters initialized by expert knowledge with the extracted data features. Third, to optimize the model's initial parameters, the projection covariance matrix adaptive evolution strategy (P-CMA-ES) algorithm is employed. Finally, a comprehensive case study is designed to verify the accuracy and effectiveness of the proposed method. The results of the case study indicate that compared with the traditional BRB method, the accuracy of the proposed model in WSN node fault diagnosis is significantly improved.
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IL-36 is known to mediate inflammation and fibrosis. Nevertheless, IL-36 signalling axis has also been implicated in cancer, although understanding of exact contribution of IL-36 to cancer progression is very limited, partly due to existence of multiple IL-36 ligands with agonistic and antagonistic function. Here we explored the role of IL-36 in oral squamous cell carcinoma (OSCC). Firstly, we analyzed expression of IL-36 ligands and receptor and found that the expression of IL-36γ was significantly higher in head and neck cancer (HNSCC) than that of normal tissues, and that the high expression of IL-36γ predicted poor clinical outcomes. Secondly, we investigated the direct effect of IL-36γ on OSCC cells and found that IL-36γ stimulated proliferation of OSCC cells with high expression of IL-36R expression. Interestingly, IL-36γ also promoted migration of OSCC cells with low to high IL-36R expression. Critically, both proliferation and migration of OSCC cells induced by IL-36γ were abrogated by anti-IL-36R mAb. Fittingly, RNA sequence analysis revealed that IL-36γ regulated genes involved in cell cycle and cell division. In summary, our results showed that IL-36γ can be a tumor-promoting factor, and targeting of IL-36R signalling may be a beneficial targeted therapy for patients with abnormal IL-36 signalling.
Sujet(s)
Carcinome épidermoïde , Tumeurs de la tête et du cou , Tumeurs de la bouche , Humains , Interleukine-1/métabolisme , Récepteurs à l'interleukine-1/génétique , Récepteurs à l'interleukine-1/métabolisme , Carcinome épidermoïde de la tête et du cou , Prolifération cellulaire , Lignée cellulaire tumoraleRÉSUMÉ
Transition metal dichalcogenides (TMDs) have been widely studied as catalysts for lithium-sulfur batteries due to their good catalytic properties. However, their poor electronic conductivity leads to slow sulfur reduction reactions. Herein, a simple Zn2+ intercalation strategy was proposed to promote the phase transition from semiconducting 2H-phase to metallic 1T-phase of MoS2. Furthermore, the Zn2+ between layers can expand the interlayer spacing of MoS2 and serve as a charge transfer bridge to promote longitudinal transport along the c-axis of electrons. DFT calculations further prove that Zn-MoS2 possesses better charge transfer ability and stronger adsorption capacity. At the same time, Zn-MoS2 exhibits excellent redox electrocatalytic performance for the conversion and decomposition of polysulfides. As expected, the lithium-sulfur battery using Zn0.12MoS2-carbon nanofibers (CNFs) as the cathode has high specific capacity (1325 mAh g-1 at 0.1 C), excellent rate performance (698 mAh g-1 at 3 C), and outstanding cycle performance (it remains 604 mAh g-1 after 700 cycles with a decay rate of 0.045% per cycle). This study provides valuable insights for improving electrocatalytic performance of lithium-sulfur batteries.
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In this study, modified biochar (BRB) was prepared from rice straw by ball milling technique and used for the adsorption of methylene blue (MB) in wastewater. The BRB was characterized by SEM, FTIR and XPS, and the adsorption model and Box-Behnken design were used to optimize the five influencing factors. The results showed that the ball milling technique could increase the content of functional groups (-OH, C=C and C-O, etc.) and aromatic structures on the surface of biochar, thus facilitating the removal of MB. The isotherm model was consistent with the Langmuir adsorption model (R2 = 0.947) and the maximum adsorption capacity was 50.27 mg/g. The adsorption kinetics was consistent with the pseudo-second-order kinetic model (R2 = 1) and the adsorption rate was mainly controlled by chemisorption. The thermodynamic model confirmed that the adsorption process was a spontaneous heat absorption reaction. The maximum adsorption efficiency was 99.78% under the optimal conditions (40â, pH 8, reaction time = 90 min, dosing amount = 0.1 mg), and the adsorption efficiency could be improved by increasing the pH and BRB dosing amount. The surface functional groups and crystal structure properties of BRB were the main determinants of adsorption, and it was clarified that physical adsorption, electrostatic attraction and π-π interaction were the main mechanisms for the adsorption of MB by BRB. The main mechanisms were clarified. Therefore, BRB is an economic, efficient and green adsorption material with good potential for the removal of dye pollutants in the aqueous environment.
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OBJECTS: Changes in condylar position and morphology after mandibular reconstruction are important to aesthetic and functional rehabilitation. We evaluated changes in condylar position and morphology at different stages after mandibular reconstruction using vascularized fibular free flap with condyle preservation. MATERIALS AND METHODS: A total of 23 patients who underwent mandibular reconstruction with fibular flap were included in this retrospective study. CT data of all patients were recorded before surgery (T0), 7 to 14 days after surgery (T1), and at least 6 months after surgery (T2). Five parameters describing the condylar position and 4 parameters describing the morphology were measured in sagittal and coronal views of CT images. The association between clinical characteristics and changes in condylar position and morphology was analyzed. A finite element model was established to investigate the stress distribution and to predict the spatial movement tendency of the condyle after reconstruction surgery. RESULTS: The condylar position changed over time after mandibular reconstruction. The ipsilateral condyles moved inferiorly after surgery (T0 to T1) and continually move anteriorly, inferiorly, and laterally during long-term follow-up (T1 to T2). Contrary changes were noted in the contralateral condyles with no statistical significance. No morphological changes were detected. The relationship between clinical characteristics and changes in condylar position and morphology was not statistically significant. A consistent result was observed in the finite element analysis. CONCLUSION: Condylar positions showed obvious changes over time after mandibular reconstruction with condylar preservation. Nevertheless, further studies should be conducted to evaluate the clinical function outcomes and condylar position. CLINICAL RELEVANCE: These findings can form the basis for the evaluation of short-term and long-term changes in condylar position and morphology among patients who have previously undergone mandibular reconstruction by FFF with condyle preservation.
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Ossification of vascular pedicle in free fibular flap for jaw reconstruction was a rare complication. The aim of our study is to evaluate its consequence and propose our clinical experience with surgical management and outcomes of this complication. Our study includes patients who underwent jaw reconstruction with free fibular flap from Jan 2017 to Dec 2021. Patients were included only they had at least one computed tomography scan in follow-up period. Among 112 cases included in our study, 3 cases were observed of abnormal ossification along vascular pedicle who underwent maxilla (two patients) or mandibular (one patient) resection. Two patients who received maxilla resection present a progressive reduction in mouth opening after surgery, and CT scans showed calcified tissue around pedicle. Surgical revision was performed in one patient. Our experience show that periosteum preserves its osteogenic capability which allows the possibility of new bone formation along the vascular pedicle. Another important factor is mechanical stress. From our experience, it was necessary to remove periosteum from vascular pedicle only when mechanical stress of vascular pedicle were high, in order to avoid complication of vascular pedicle calcification. Surgical excision of calcification may be necessary only with clinical symptom. We believe this study could aid in understanding of pedicle ossification and contribute towards prevention and treatment of pedicle ossification.
Sujet(s)
Lambeaux tissulaires libres , Reconstruction mandibulaire , Ossification hétérotopique , Calcification vasculaire , Humains , Lambeaux tissulaires libres/vascularisation , Ostéogenèse , Ossification hétérotopique/imagerie diagnostique , Ossification hétérotopique/étiologie , Ossification hétérotopique/chirurgie , Complications postopératoires , Fibula , Reconstruction mandibulaire/effets indésirablesRÉSUMÉ
OBJECTIVES: This study investigate the clinical and imaging features of Ewing sarcoma (ES) of the jaw. METHODS: Eight cases of pathologically diagnosed ES of the jaw from January 2010 to June 2022 were included in the study. Clinical and radiological features were retrospectively analyzed. RESULTS: Among the eight cases, the mean age at onset was 29.4 years, and the male to female ratio was 7â¶1. The predilecting site was the posterior part of mandible, accounting for 75% of the cases. The lesions often exhibited early numbness of the lower lip and lymphadenopathy. The main radiographic manifestation of mandibular lesions was ill-defined radiolucency, mixed with fibrous or brush-like tumor matrix, and soft tissue mass. The maxillary ES lesions mainly presented as lytic bone destruction accompanied by adjacent soft tissue mass. Periosteal ossification was rarely seen. CONCLUSIONS: The clinical and imaging characteristics of ES in the jaw are helpful for its diagnosis.
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Tumeurs osseuses , Sarcome d'Ewing , Mâle , Humains , Femelle , Sarcome d'Ewing/imagerie diagnostique , Sarcome d'Ewing/anatomopathologie , Études rétrospectives , Radiographie , Mandibule/anatomopathologie , LèvreRÉSUMÉ
The effect of steel fibers (0-1.5% by volume) and polypropylene fibers (0-0.5% by volume) on chloride transport in mortars under unsaturated and saturated conditions was investigated using a natural immersion method. Moreover, the micromorphology of the fiber-mortar interface and the pore structure of fiber reinforced mortars were detected using scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP), respectively. The results show that both of the steel fibers and polypropylene fibers have an insignificant effect on the chloride diffusion coefficient of mortars, no matter under unsaturated or saturated conditions. The incorporation of steel fibers has no obvious action on the pore structure of mortars, and the interfacial zone around the steel fibers is not a preferential path for chloride transport. However, the addition of 0.1-0.5% polypropylene fibers refines the pore size of mortars, and yet slightly increases the total porosity. The polypropylene fiber-mortar interface is insignificant, while the agglomerate of polypropylene fibers exists.
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Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions, with a high rate of metastasis. Cancer-associated fibroblasts (CAFs) play critical roles in tumor growth, metastasis and invasion, making them attractive therapeutic targets for cancer treatment. As an old anti-coccidiosis drug for poultry, Halofuginone (HF) has also been reported to possess anti-fibrosis and anti-cancer activities in the recent decades. However, whether it works by targeting CAFs in OSCC, and the mechanisms involved remain unclear. In the present study, we observed HF dose-dependently inhibits OSCC-derived CAF viability and proliferation. Meanwhile, HF decreased the expressions of α-SMA, FSP-1 and PDGFRß, markers of the malignant phenotype of CAFs, both at mRNA and protein levels. Furthermore, functional studies demonstrated that HF dramatically attenuates the promotion effect of CAFs on OSCC cell migration and invasion. Mechanistically, the inhibition of MMP2 secretion and the upstream TGF-ß/Smad2/3 signaling pathway played an important role in these processes. In the orthotopic transplanted tongue carcinoma in mice model, we confirmed that HF administration inhibited tumor growth and lymph node metastasis (LNM) with reduced CAF population, MMP2 expression and collagen deposition in tumor. Altogether, these results indicate that HF can inhibit the migration and invasion of OSCC by targeting CAFs, which will provide new ideas for the treatment of OSCC.
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Effective fault-diagnosis strategies have been the focus of research on multi-agent systems (MASs). In this paper, the belief rule base (BRB)-based distributed fault-diagnosis problem for MASs is investigated, and a topology-switching strategy is developed to increase the reliability of fault-diagnosis model. Firstly, a BRB-based distributed fault-diagnosis model is constructed for the MAS with multiple faults, then expert knowledge is used to judge whether the agent is faulty. Then, considering that the system may be influenced by the fault or some other factors and thus leading to a decrease in the accuracy of the fault-diagnosis results, a topology-switching strategy based on the average distance of the output diagnosis accuracy is proposed to update the topology of the agent so that the fault-diagnosis results can be more reliable. Note that the topology-switching threshold is designed based on the average distance between the accuracy of the fault diagnosis of each agent. The method proposed in this paper can solve the problem when the fault-diagnosis accuracy of the model is affected by some common factors and thus decreases, and can improve the reliability of the fault-diagnosis model very well. Finally, the effectiveness of the BRB-based distributed fault-diagnosis model and the proposed topology-switching strategy to improve the fault-diagnosis accuracy is verified by simulation examples.
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Wireless sensor network (WSN) is inevitably subject to node failures due to their harsh operating environments and extra-long working hours. In order to ensure reliable and correct data collection, WSN node fault diagnosis is necessary. Fault diagnosis of sensor nodes usually requires the extraction of data features from the original collected data. However, the data features of different types of faults sometimes have similarities, making it difficult to distinguish and represent the types of faults in the diagnosis results, these indistinguishable types of faults are called ambiguous information. Therefore, a belief rule base with power set (PBRB) fault diagnosis method is proposed. In this method, the power set identification framework is used to represent the fuzzy information, the evidential reasoning (ER) method is used as the reasoning process, and the projection covariance matrix adaptive evolution strategy (P-CMA-ES) is used as the parameter optimization algorithm. The results of the case study show that PBRB method has higher accuracy and better stability compared to other commonly used fault diagnosis methods. According to the research results, PBRB can not only represent the fault types that are difficult to distinguish, but also has the advantage of small sample training. This makes the model obtain high fault diagnosis accuracy and stability.
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An early diagnosis of salivary gland tumors (SGTs) and determination of their malignancy are conducive to developing individualized therapeutic strategies and thus improving prognosis. The aim of this study was to investigate the difference of serum metabolic profiles in patients with SGTs to better understand the mechanism of this disease and disease risk stratification. We used ultrahigh-performance liquid chromatography Q Exactive mass spectrometry and multivariate statistical analyses to conduct a comprehensive analysis of serum metabolites in a population with normal control and SGTs. 32 differentially expressed metabolites were identified, while the level of serine and lactic acid were investigated to gradually upregulate in benign SGTs and malignant SGTs. Then, the expression of serine and lactic acid were assessed in validation cohort using multiple reaction monitoring (MRM) based targeted metabolite analysis. A risk score formula based on the amount of serine and lactic acid was developed and explored to be significantly related to benign SGTs and malignant SGTs in discovery and validation cohort. Our work highlights the possible use of the risk score assessment based on the serum metabolites not only reveal in the early diagnosis of SGTs but also assist in enhancing current therapeutic strategies in the clinic.
Sujet(s)
Tumeurs des glandes salivaires , Humains , Acide lactique , Métabolomique , Pronostic , Tumeurs des glandes salivaires/diagnostic , Tumeurs des glandes salivaires/métabolisme , Tumeurs des glandes salivaires/anatomopathologie , SérineRÉSUMÉ
BACKGROUND: Metastatic adenocarcinoma of the jaw (MAJ) is a rare disease that accounts for 1%-3% of all oral and maxillofacial malignant tumours. Oral and maxillofacial pain may be the first symptom of metastatic spread of an occult primary tumour. Therefore, early identification of oral and maxillofacial pain by dental professionals is critical. AIM: To explore the clinical and computerized tomography (CT) features of MAJ with oral and maxillofacial pain as the first symptom. METHODS: The medical records of all patients who were treated in our hospital between January 2006 and February 2020, and diagnosed with MAJ with oral and maxillofacial pain as the first symptom, were reviewed retrospectively. Clinical data were collected on age, sex, medical history, clinical manifestations, site of metastasis, and site of the primary lesion. CT features were analysed in detail, and a radiological classification scheme comprising five types: Osteolytic, osteoblastic, mixed, cystic, and alveolar bone resorption was proposed. RESULTS: The primary sites of MAJ were the lungs (n = 6), liver (n = 4), kidneys (n = 2), prostate (n = 1), and gastric cardia (n = 1). Five tumours were classified as the osteolytic type, all with a permeative margin (100%, P < 0.05), and three were classified as the mixed type, mostly with a moth-eaten margin (80%, P < 0.05). The cystic (n = 3) and alveolar bone resorption (n = 1) types had geographic margins, and the osteoblastic type (n = 1) had sclerotic margins. Moreover, nine tumours showed periosteal reaction and five showed a localised soft tissue mass, while the occurrence of jaw expansion was relatively rare. CONCLUSION: MAJ has complex clinical and CT features. Oral and maxillofacial pain may be the first sign of a primary tumour affecting other sites.
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Background: Advanced oral squamous cell carcinoma (OSCC) has large lesions and deep infiltration, and the control of safe surgical margins was difficult. If residual tumor remains after incomplete tumor resection, it can lead to local tumor recurrence or even distant metastasis. This study sought to investigate the clinical application of indocyanine green (ICG)-based near-infrared fluorescence (NIF) molecular imaging in the intraoperative detection of surgical margins of advanced OSCC. Methods: Twenty-nine patients with advanced OSCC treated at the First Ward of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital were divided into the ICG group and non-ICG group. In the ICG group, the tumors were removed with the assistance of ICG fluorescence navigation technology. In the non-ICG group, the tumors were removed with conventional methods, and the cutting-edge tissues of the two groups underwent frozen biopsies. The margin abnormality rates were calculated and compared. Results: Under the excitation of NIF in the ICG group, tumor fluorescence development was observable in all lesions, and the tumor boundary was clear. The abnormal rates of the incisional margin in the ICG group and non-ICG group were 0.78% and 6.25%, respectively (P<0.05). Conclusions: ICG-mediated NIF imaging technology provides a new method for observing and completely resecting tumors under direct vision during operation, and finding residual tumors at the cutting edge in time. These results will inform the treatment of advanced OSCC.
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INTRODUCTION: Complex ectopic drainage of body veins is a rare congenital disease. Its preoperative diagnosis and surgical choice can be considerable challenges. CASE SUMMARY: A 5-year-old patient was diagnosed precisely by preoperative transthoracic echocardiography, computed tomography (CT), three-dimensional (3D) reconstruction, and three-dimensional (3D) printing of the heart and great blood vessels. The operation was performed successfully using flexible intraoperative intubation strategies. CONCLUSION: 3D printing technology can assist in the formulation of surgical protocols for complex body vein ectopic drainage. Flexible intubation strategies can increase the success of the operation.
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BACKGROUND: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. MATERIALS: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients' tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. RESULTS: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2TCs) and FLCs (PLOD2FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2FLCs rather than PLOD2TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial-mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. CONCLUSIONS: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy.
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Carcinome épidermoïde/anatomopathologie , Lysine/métabolisme , Tumeurs de la bouche/anatomopathologie , Procollagen-lysine, 2-oxoglutarate 5-dioxygenase/génétique , Procollagen-lysine, 2-oxoglutarate 5-dioxygenase/métabolisme , Régulation positive , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Carcinome épidermoïde/génétique , Carcinome épidermoïde/métabolisme , Lignée cellulaire tumorale , Survie sans rechute , Transition épithélio-mésenchymateuse , Femelle , Régulation de l'expression des gènes tumoraux , Humains , Métastase lymphatique , Mâle , Spectrométrie de masse , Tumeurs de la bouche/génétique , Tumeurs de la bouche/métabolisme , Stadification tumorale , PronosticRÉSUMÉ
BACKGROUND: Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation in GATA4 accounting for the etiology in a Chinese family with ASD. METHODS: We identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members. RESULTS: Direct sequencing of GATA4 from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutation GATA4 (c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD). CONCLUSIONS: We identified for the first time a novel M310T mutation in the GATA4 gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.
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Troubles du rythme cardiaque/génétique , Facteur de transcription GATA-4/génétique , Communications interauriculaires/génétique , Mutation , Adolescent , Adulte , Sujet âgé , Troubles du rythme cardiaque/diagnostic , Troubles du rythme cardiaque/physiopathologie , Enfant , Enfant d'âge préscolaire , Biologie informatique , Analyse de mutations d'ADN , Femelle , Prédisposition génétique à une maladie , Communications interauriculaires/diagnostic , Communications interauriculaires/physiopathologie , Hérédité , Séquençage nucléotidique à haut débit , Humains , Mâle , Adulte d'âge moyen , Pedigree , Phénotype ,RÉSUMÉ
To solve the problems of low early strength and severe plastic cracking caused by high volume fly ash used in cement-based materials. Triethanolamine (TEA), calcium hydroxide (Ca(OH)2), and sodium silicate (Na2SiO3) or sodium sulfate (Na2SO4) were selected to conduct a ternary doping test. The compressive strength of samples was measured to determine the best ratio, content, and time effect of the activator, and its action mechanism was studied by various micro test. The quantitative calculation model of main hydration products was established in the fly ash-cement system. Based on the simulation of molecular dynamics, the structure of NASH gel was studied under alkali activation. The results show that the optimal mixing mass ratio of TEA:Ca(OH)2:Na2SiO3 is 2:75:25 and the optimal dosage is 1.02% of the cementitious material. There are a large number of needle-like ettringite, petaloid hydrated calcium aluminate and clusters of hydrated calcium silicate gel in the system, whereas the amount of plate-like CH decreased significantly at hydration for 14 days. The Si/Al is three and aluminium coordination is predominantly tetrahedral, and the order of bonds stability and atoms mobility are Si-O > Al-O > Na-O and Na > O > Al> in the NASH gel, respectively. Under the Na+ and alkali environment, the Si(OH)4 and Al(OH)4- formed polycondensation reaction to reform polymers Si-O-Si and Al-O-Si, forming a large amount of NASH gel.