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2D materials with atomic thickness display strong gate controllability and emerge as promising materials to build area-efficient electronic circuits. However, achieving the effective and nondestructive modulation of carrier density/type in 2D materials is still challenging because the introduction of dopants will greatly degrade the carrier transport via Coulomb scattering. Here, a strategy to control the polarity of tungsten diselenide (WSe2 ) field-effect transistors (FETs) via introducing hexagonal boron nitride (h-BN) as the interfacial dielectric layer is devised. By modulating the h-BN thickness, the carrier type of WSe2 FETs has been switched from hole to electron. The ultrathin body of WSe2 , combined with the effective polarity control, together contribute to the versatile single-transistor logic gates, including NOR, AND, and XNOR gates, and the operation of only two transistors as a half adder in logic circuits. Compared with the use of 12 transistors based on static Si CMOS technology, the transistor number of the half adder is reduced by 83.3%. The unique carrier modulation approach has general applicability toward 2D logic gates and circuits for the improvement of area efficiency in logic computation.
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Exosomes, small extracellular vesicles that function as a key regulator of cell-to-cell communication, are emerging as a promising candidate for bone regeneration. Here, we aimed to investigate the effect of exosomes from pre-differentiated human alveolar bone-derived bone marrow mesenchymal stromal cells (AB-BMSCs) carrying specific microRNAs on bone regeneration. Exosomes secreted from AB-BMSCs pre-differentiated for 0 and 7 days were cocultured with BMSCs in vitro to investigate their effect on the differentiation of the BMSCs. MiRNAs from AB-BMSCs at different stages of osteogenic differentiation were analyzed. BMSCs seeded on poly-L-lactic acid(PLLA) scaffolds were treated with miRNA antagonist-decorated exosomes to verify their effect on new bone regeneration. Exosomes pre-differentiated for 7 days effectively promoted the differentiation of BMSCs. Bioinformatic analysis revealed that miRNAs within the exosomes were differentially expressed, including the upregulation of osteogenic miRNAs (miR-3182, miR-1468) and downregulation of anti-osteogenic miRNAs (miR-182-5p, miR-335-3p, miR-382-5p), causing activation of the PI3K/Akt signaling pathway. The treatment of BMSC-seeded scaffolds with anti-miR-182-5p decorated exosomes demonstrated enhanced osteogenic differentiation and efficient formation of new bone. In conclusion, Osteogenic exosomes secreted from pre-differentiated AB-BMSCs were identified and the gene modification of exosomes provides great potential as a bone regeneration strategy. DATA AVAILABILITY STATEMENT: Data generated or analyzed in this paper partly are available in the GEO public data repository(http://www.ncbi.nlm.nih.gov/geo).
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Osteogênese , Exossomos/genética , Exossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regeneração Óssea/genética , Células-Tronco Mesenquimais/metabolismo , Diferenciação CelularRESUMO
Two-dimensional (2D) PdSe2film has the characteristics of adjustable bandgap, high carrier mobility, and high stability. Photodetector (PD) based on 2D PdSe2exhibits wide spectral self-driving features, demonstrating enormous potential in the field of optical detection. Here, we design and fabricate PdSe2/Si heterojunction PDs with various thicknesses of the PdSe2films from 10 to 35 nm. Due to the enhancement of light absorption capacity and built-in electric field of heterojunction, the photodetector with thicker PdSe2film can generate more photo-generated carriers and effectively separate them to form a large photocurrent, thus showing more excellent photodetection performance. The responsivity and specific detectivity of the PdSe2/Si PDs with 10 nm, 20 nm, and 35 nm PdSe2films are 2.12 A W-1and 6.72 × 109Jones, 6.17 A W-1and 1.95 × 1010Jones, and 8.02 A W-1and 2.54 × 1010Jones, respectively (808 nm illumination). The PD with 35 nm PdSe2film exhibits better performance than the other two PDs, with the rise/fall times of 15.8µs/138.9µs atf= 1 kHz and the cut-off frequency of 8.6 kHz. Furthermore, we demonstrate that the properties of PdSe2/Si PD array have excellent uniformity and stability at room temperature and shows potential for image sensing in the UV-vis-NIR wavelength range.
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MicroRNA (miR)-23b-3p is known to target various genes that are involved in cancer-related pathways. Exosomes are emerging intercellular communication agents. Exosomes secreted by cancer cells can deliver active molecules to the surrounding stromal cells, thereby influencing the recipient cells and promoting the development of cancers. However, the role of exosomal miR-23b-3p in salivary adenoid cystic carcinoma (SACC) is not yet clear. In this study, we set out to investigate the potential role of cancer-derived exosomal miR-23b-3p-related phosphatase and tensin homolog deleted on chromosome 10 in the alteration of angiogenesis and vascular permeability in SACC. We investigated the effect of exosomal miR-23b-3p on the progression of SACC. In vitro experiments indicated that exosomal miR-23b-3p led to an upregulation of vascular permeability, and reduced expression of tight junction proteins. In addition, exosomal miR-23b-3p also enhanced angiogenesis and migration. Next, the angiogenic effect of exosomal miR-23b-3p was validated in vivo, as it led to an increase in the tumor microvasculature. Furthermore, the growth rate of SACC was faster after injection of exosomes loaded with cholesterol-modified miR-23b-3p in mice. In conclusion, these results revealed that SACC cell-derived exosomes play an important role in promoting angiogenesis and local vascular microleakage of SACC by transporting miR-23b-3p, which suggests that miR-23b-3p in the exosomes may be a potential biomarker for distant metastasis of SACC. This suggests the potential of a novel therapeutic target by delivering anti-miR-23b-3p that focuses on exosomes.
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Carcinoma Adenoide Cístico , Exossomos , MicroRNAs , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias das Glândulas Salivares , Animais , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neoplasias das Glândulas Salivares/metabolismoRESUMO
BACKGROUND: Metabolic disorders are significant in the occurrence and development of malignant tumors. Changes of specific metabolites and metabolic pathways are molecular therapeutic targets. This study aims to determine the metabolic differences between oral squamous cell carcinoma (OSCC) tissues and paired adjacent noncancerous tissues (ANT) through liquid chromatography-mass spectrometry (LC-MS). SPHK1 is a key enzyme in sphingolipid metabolism. This study also investigates the potential role of SPHK1 in OSCC. MATERIALS AND METHODS: This study used LC-MS to analyze metabolic differences between OSCC tissues and paired ANT. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied to explain the significance of phospholipid metabolism pathways in the occurrence and development of OSCC. Through further experiments, we confirmed the oncogenic phenotypes of SPHK1 in vitro and in vivo, including proliferation, migration, and invasion. RESULTS: The sphingolipid metabolic pathway was significantly activated in OSCC, and the key enzyme SPHK1 was significantly upregulated in oral cancer tissues, predicting poor OSCC prognosis. In this study, SPHK1 overexpression was associated with high-grade malignancy and poor OSCC prognosis. SPHK1 targeted NF-κB by facilitating p65 expression to regulate OSCC tumor progression and promote metastasis. CONCLUSIONS: This study identified metabolic differences between OSCC and paired ANT, explored the carcinogenic role of overexpressed SPHK1, and revealed the association of SPHK1 with poor OSCC prognosis. SPHK1 targets NF-κB signaling by facilitating p65 expression to regulate tumor progression and promote tumor metastasis, providing potential therapeutic targets for diagnosing and treating oral tumors.
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Neoplasias Bucais , Fosfotransferases (Aceptor do Grupo Álcool) , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/patologia , NF-kappa B/metabolismo , Fosfolipídeos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Esfingolipídeos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
BACKGROUND: miRNAs and mRNAs have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop the pivotal miRNA biomarkers-based prognostic signature for salivary adenoid cystic carcinoma. METHODS: The miRNA and mRNA expression data were integrated from the gene expression omnibus database to study their involvement in salivary adenoid cystic carcinoma development and progression. Gene ontology and kyoto encyclopedia of genes and genomes were conducted to analyze the biological pathways. Reverse transcription-quantitative PCR was used to verify the expression of selected miRNAs in salivary adenoid cystic carcinoma and corresponding normal tissues. RESULTS: There were 386 differentially expressed genes: 158 upregulated and 228 downregulated genes and 102 differentially expressed miRNAs: 78 upregulated and 24 downregulated miRNAs in the salivary adenoid cystic carcinoma samples. A miRNA-mRNA network containing 11 miRNAs and 199 genes was subsequently constructed. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the genes targeted by the 11 miRNAs were mostly involved in tumor-related pathways and processes, such as miRNAs in cancer, focal adhesion, neurotrophin signaling pathway, and the PI3K-Akt signaling pathway. Among them, 4 miRNAs (miR-375, miR-494, miR-34c-5p, and miR-331-3p) were selected to verify by reverse transcription-quantitative PCR in 36 pairs of collected salivary adenoid cystic carcinoma and adjacent nontumor samples. Overall survival analysis revealed that the higher expression of miR-331-3p was significantly associated with a worst overall survival and multivariate Cox regression analysis suggested that hsa-miR-331-3p could be an independent prognostic factor for salivary adenoid cystic carcinoma. CONCLUSION: Our results revealed that 4-miRNAs signature was a powerful prognostic biomarker for salivary adenoid cystic carcinoma, which provide a basis for exploring deeper mechanisms regarding the progression of salivary adenoid cystic carcinoma, and leading to the development of potential therapeutic strategies.
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Carcinogênese/genética , Carcinoma Adenoide Cístico , MicroRNAs , Neoplasias das Glândulas Salivares , Carcinoma Adenoide Cístico/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases , Neoplasias das Glândulas Salivares/genéticaRESUMO
Infrared optoelectronic devices are capable of operating in harsh environments with outstanding confidentiality and reliability. Nevertheless, suffering from the large band gap value, most semiconductor materials are difficult to detect infrared light signals. Here, Mg2Si/Si heterojunction photodetectors (PDs), which possess the advantages of low-cost, easy process, environmental friendliness, and compatibility with silicon CMOS technology, have been reported with a broadband spectral response as tested from 532 to 1550 nm under zero-bias. When the incident light wavelength is 808 nm, the Mg2Si/Si photodetector (PD) has a responsivity of 1.04 A W-1and a specific detectivity of 1.51 × 1012Jones. Furthermore, we find that the Ag nanoparticles (Ag_NPs) assembled on the Mg2Si layer can greatly improve the performance of the Mg2Si/Si PD. The responsivity and specific detectivity of Mg2Si/Si device with Ag_NPs under 808 nm illumination are 2.55 A W-1and 2.60 × 1012Jones, respectively. These excellent photodetection performances can be attributed to the high-quality of our grown Mg2Si material and the strong built-in electric field effect in the heterojunction, which can be further enhanced by the local surface plasmon effect and local electromagnetic field induced by Ag_NPs. Our study would provide significant guidance for the development of new self-powered infrared PDs based on silicon materials.
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There is great interest in the incorporation of novel two-dimensional materials into Si-based technologies to realize multifunctional optoelectronic devices via heterogeneous integration. Here, we demonstrate a gate-tunable, self-driven, high-performance broadband phototransistor array based on a PdSe2/Si Schottky junction, which is fabricated by pre-depositing a semi-metallic PdSe2 film on a SOI substrate. In addition, thanks to the zero bandgap of the PdSe2 material and the PdSe2/Si vertical heterostructure, the prepared phototransistor exhibits pronounced photovoltaic properties in a wide spectral range from ultraviolet to near-infrared. The responsivity, specific detectivity and response time of the device at the incident light wavelength of 808 nm are 1.15 A W-1, 9.39 × 1010 Jones, and 27.1/40.3 µs, respectively, which are better than those of previously reported PdSe2-based photodetectors. The photoelectric performance can be further improved by applying an appropriate gate voltage to the phototransistor and the responsivity of the device increases to 1.61 A W-1 at VG = 5 V. We demonstrate the excellent imaging capabilities of a 4 × 4 array image sensor using PdSe2/SOI phototransistors under 375 nm, 532 nm, and 808 nm laser sources.
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PURPOSE: To investigate the feasibility and safety of the deep circumflex iliac artery (DCIA) derived chimeric flap through the anatomical study of the blood vessels and perforating branches in the ilioinguinal region, and to provide the basis for selecting different DCIA chimeric flap schemes according to the difficulty of surgery, defect conditions and repair needs. METHODS: Six Chinese adult specimens were dissected by retrograde perfusion of red latex into bilateral femoral arteries. At the same time, the length, diameter and main branch position of DCIA vascular pedicle were measured in 12 lower limb CTAs, and compared with the anatomical data. Six patients with oral tumors accompanied by mandibular defects who were treated in the Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University from July 2020 to November 2021 were repaired and reconstructed with the chimeric iliac myofascial flap. The postoperative appearance and occlusal function of the recipient area were observed. SPSS 19.0 software package was used for data analysis. RESULTS: A total of 19 DCIA perforators with an external diameter of ≥ 0.5 mm were found in 12 specimens of ilioinguinal region. These perforators were distributed in the 5 cm×3 cm area, inside the ilium and 5cm behind the anterior superior iliac spine. The length of DCIA vascular pedicle was (6.73±1.06) cm. The measured value of the external diameter of the starting position of the vascular pedicle was (2.55±0.29) mm. The outer diameter of DCIA skin perforator penetrating deep fascia was (1.12±0.14) mm. In the CTA analysis of 12 lower limbs, it was found that the length of DCIA vascular pedicle was (6.98±0.62) cm. The measured diameter at the original position of vascular pedicle was (2.35±0.20) mm. Six cases of mandibular defects were repaired with iliac internal oblique fascia mosaic flap. Six cases of lliac flap survived successfully after operation. Follow up for 6 to 24 months (average 12 months) showed that the mandibular shape and function recovered well, the intraoral myofascial flap became mucosal, and the implanted iliac bone showed no significant volume change on CT after operation. Walking and weight bearing in donor area were basically normal, and no abdominal hernia occurred. CONCLUSIONS: DCIA and its main branches have a relatively constant course and distribution in the ilioinguinal region. According to the conditions of different defect areas, different tissue types of chimeric flaps based on DCIA can be prepared to meet the repair requirements. The donor site complications can be controlled, and it is an ideal choice to repair mandibular defects.
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Procedimentos de Cirurgia Plástica , Adulto , Humanos , Ílio , Retalhos Cirúrgicos/irrigação sanguínea , Coxa da Perna , MúsculosRESUMO
Salivary adenoid cystic carcinoma (SACC) is a rare malignant tumor of the salivary gland. Studies have suggested that miRNA may play a crucial role in the invasion and metastasis of SACC. This study aimed to investigate the role of miR-200b-5p in SACC progression. Reverse transcription-quantitative PCR and western blot assay were used to detect the expression levels of miR-200b-5p and BTBD1. The biological functions of miR-200b-5p were evaluated via wound-healing assays, transwell assays, and xenograft nude mice model. The interaction between miR-200b-5p and BTBD1 was assessed using luciferase assay. Results showed that miR-200b-5p was downregulated in the SACC tissues while BTBD1 was upregulated. miR-200b-5p overexpression suppressed SACC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Bioinformatics prediction and luciferase reporter assay revealed that miR-200b-5p could directly bind to BTBD1. Besides, miR-200b-5p overexpression could rescue the tumor-promoting effect of BTBD1. miR-200b-5p inhibited tumor progression by modulating EMT-related proteins, targeting BTBD1 and inhibiting PI3K/AKT signaling pathway. Overall, our findings indicate that miR-200b-5p can suppress SACC proliferation, migration, invasion, and EMT by regulating BTBD1 and PI3K/AKT axis, providing a promising therapeutic target for SACC treatment.
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Carcinoma Adenoide Cístico , MicroRNAs , Neoplasias das Glândulas Salivares , Animais , Camundongos , Humanos , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Invasividade Neoplásica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Abnormal expression of the potassium channel tetramerization domain containing 12 (KCTD12) is closely related to the occurrence and development of various tumors, but a pan-cancer analysis of KCTD12 has not yet been conducted. We explored the association between KCTD12 and more than 30 human malignancies using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. First, the mRNA and protein levels of KCTD12 were examined and their correlations with tumor stage and survival were explored. Second, we analyzed the infiltration of CD8+ and CD4+ T cells and cancer-associated fibroblasts in tumors and explored the correlation between KCTD12 expression and tumor cell stemness, genomic heterogeneity, and diagnostic specificity. Finally, we explored the molecular mechanisms associated with KCTD12 using KEGG/GO analysis. The results showed that KCTD12 mRNA and protein expression levels decreased in most tumors was significantly associated with the prognosis of tumor patients, and the phosphorylation level of KCTD12 decreased in several tumors, such as S200 and T196, pancreatic adenocarcinoma (PAAD), lung adenocarcinoma (LUAD), and breast invasive cancer (BRCA). The expression of KCTD12 was positively correlated with the degree of cancer-associated fibroblasts infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), PAAD, and stomach adenocarcinoma (STAD). The relationship between KCTD12 expression and CD8+ and CD4+ T cell infiltration was also clarified. KCTD12 showed high diagnostic sensitivity for various types of tumors and may be involved in tumor cell biology by affecting tumor cell stemness, tumor burden, and other characteristics. Finally, we analyzed the molecular functions of KCTD12 and possible KEGG/GO signaling pathways. In this study, we developed a biological marker for diagnosis, prognosis, and immune infiltration of the pan-cancers.
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Adenocarcinoma , Neoplasias da Mama , Neoplasias Pulmonares , Neoplasias Pancreáticas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias PancreáticasRESUMO
Ameloblastic fibro-odontosarcoma (AFOS) now designated as odontogenic sarcoma is an extremely rare odontogenic tumor, which histologically presents as a biphasic neoplasm with a malignant mesenchymal component plus ameloblastic epithelium. Here we report a 27-year-old Chinese female with the complaint of a painful swelling for half a month in the right mandible. A segmental mandibulectomy, with an immediate mandibular reconstruction using a free vascularized osteocutaneous fibular flap was performed using surgical guide models. Histological analysis revealed a primary odontogenic sarcoma. The postoperative period was uneventful, and no clinical indication of recurrence or metastasis was observed during the 3-year follow-up. No adjuvant therapy was proposed. This is the first odontogenic sarcoma case reported in China after the new World Health Organization classification of odontogenic lesions.
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Studies have shown the inhibitory effect of microRNA-34a on proliferation, migration, and invasion of oral squamous cell carcinoma. However, the lack of a safe and effective delivery system limits the clinical application of microRNA-34a in oral cancer treatment. An exosome is a small extracellular vesicle that mediates intercellular communication by delivering proteins, nucleic acids, and other contents, and functions as a natural drug delivery carrier. Here, we aimed to explore whether exosomes could be used to load microRNA-34a via co-incubation and further used to treat OSCC. Ultracentrifugation was used to obtain exosomes derived from HEK293T cells and the extracted exosomes were analyzed via transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Subsequently, we loaded cholesterol-modified microRNA-34a into HEK293T cell exosomes by co-incubation. Then, PKH67 and Cy3 co-labeled exo-microRNA-34a were co-incubated with HN6 cells and exosome entry into the HN6 cells was observed using a confocal laser scanning microscope. The cell proliferation, migration, and invasion were assessed by CCK-8 and Transwell assay analysis. SATB2 expression in HN6 cells was analyzed via western blotting. In this study, cholesterol-modified microRNA-34a was loaded into exosomes of HEK293T cells by co-incubation. The microRNA-34a-loaded exosomes were secreted from HEK293T cells and were absorbed by HN6 oral squamous carcinoma cells. Further, microRNA-34a-loaded exosomes led to a significant inhibition of HN6 cell proliferation, migration, and invasion by down regulating SATB2 expression. These results report a new delivery method for microRNA-34a, providing a new approach for the treatment of oral cancer.
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Carcinoma de Células Escamosas , Exossomos , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Exossomos/metabolismo , Células HEK293 , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismoRESUMO
OBJECTIVE: The current study aimed to explore the effect of Follistatin-like 1 (FSTL1) on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in an inflammatory environment. DESIGN: Animal models of FSTL1-deficiency and wild-type mice were used, and the micro-CT images of the femoral head were evaluated. Mouse bone marrow mesenchymal stem cells were treated with various concentrations of recombinant FSTL1 (rFSTL1) in an inflammatory environment in vitro. Meanwhile, overexpression or knockdown of FSTL1 through lentiviral transfection was performed. Alkaline phosphatase (ALP) activity was tested, and Alizarin Red staining (ARS) was performed to evaluate osteogenic differentiation ability. The mRNA expression level of osteogenesis-related genes was detected by RT-qPCR. RESULTS: In vivo experiments revealed a higher number of femoral skulls, higher trabecular thickness, smaller trabecular space, and less osteoporosis in FSTL1-knockdown mice than in the wild-type mice. The BMSCs with overexpression of FSTL1 or those treated with recombinant FSTL1 (rFSTL1) showed suppression of ALP activity, calcium nodule formation, and expression of osteogenesis-related genes osteopontin (OPN), osteocalcin (OCN), collagen type I alpha 1 (Col1α1), and more importantly, rFSTL1 functions in a dose-dependent manner. In contrast, FSTL1 knockdown promoted the osteogenesis activity and the expression of these osteogenesis-related genes in vitro. CONCLUSIONS: FSTL1 is an osteogenic suppressor that inhibits the osteogenic differentiation of BMSCs during inflammation and it can be a new target for bone regeneration.
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Diferenciação Celular , Proteínas Relacionadas à Folistatina/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteogênese , Animais , Células da Medula Óssea , Células Cultivadas , Inflamação , CamundongosRESUMO
Two-dimensional (2D) materials with the atomically thin thickness have attracted great interest in the post-Moore's Law era because of their tremendous potential to continue transistor downscaling and offered advances in device performance at the atomic limit. However, the metal-semiconductor contact is the bottleneck in field-effect transistors (FETs) integrating 2D semiconductors as channel materials. A robust and tunable doping method at the source and drain region of 2D transistors to minimize the contact resistance is highly sought after. Here we report a stable carrier doping method via the mild covalent grafting of maleimides on the surface of 2D transition metal dichalcogenides. The chemisorbed interaction contributes to the efficient carrier doping without degrading the high-performance carrier transport. Density functional theory results further illustrate that the molecular functionalization leads to the mild hybridization and the negligible impact on the conduction bands of monolayer MoS2, avoiding the random scattering from the dopants. Differently from reported molecular treatments, our strategy displays high thermal stability (above 300 °C) and it is compatible with micro/nano processing technology. The contact resistance of MoS2 FETs can be greatly reduced by â¼12 times after molecular functionalization. The Schottky barrier of 44 meV is achieved on monolayer MoS2 FETs, demonstrating efficient charge injection between metal and 2D semiconductor. The mild covalent functionalization of molecules on 2D semiconductors represents a powerful strategy to perform the carrier doping and the device optimization.
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To develop a shapable bulk antibacterial nanocomposite biomaterial for bone regeneration. A bulk agarose-gelatine hydrogel was mineralized using a hydrogel mineralizing system aided with electrophoresis, and the mineralized hydrogel was loaded with minocycline to obtain the agarose-gelatine-hydroxyapatite-minocycline nanocomposite. The nanocomposite had a large Brunauer-Emmett-Teller surface area of 44.4518 m2g-1and a high porosity of 76.9%. Hydroxyapatite crystals were well developed in the hydrogel matrix and exhibited a hybrid structure of microscale and nanoscale motifs. The addition of minocycline resulted in a continuous antibiotic release, inhibiting the growth ofStaphylococcus aureusover 2 weeksin vitro. Exposed to rabbit bone marrow mesenchymal stem cells, the nanocomposite revealed good cytocompatibilityin vitro. Furthermore, the biomaterial could effectively enhance the bone regeneration in a critical-size rabbit cranial defect modelin vivo. These findings depicted that the nanocomposite, with good biocompatibility and good antibacterial property, is a promising candidate for future clinical application in bone tissue engineering or as a prospective bone replacement biomaterial.
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Durapatita , Nanocompostos , Animais , Regeneração Óssea , Durapatita/química , Eletroforese , Gelatina/química , Minociclina , Nanocompostos/química , Osteogênese , Estudos Prospectivos , Coelhos , Sefarose , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
The progression of salivary adenoid cystic carcinoma (SACC) is closely related to abnormal gene expression. Herein, the role of Sphk1 in SACC was explored. Sphk1 was overexpressed in SACC tissues. In SACC cell lines, Sphk1 induced cell proliferation, inhibited apoptosis, and promoted cell migration. Moreover, Sphk1 overexpression induced up-regulation of the PI3K protein level and AKT phosphorylation level. Rescue assays further showed that activation of the Sphk1 /PI3K/Akt pathway affected various biological functions of SACC cells. Together, these findings suggested that Sphk1 promotes salivary tumorigenesis by activating the PI3K/ Akt pathway, which may provide novel intervention targets for SACC treatment.
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Carcinoma Adenoide Cístico/enzimologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias das Glândulas Salivares/enzimologia , Apoptose , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Fosforilação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Transdução de SinaisRESUMO
While atypical expression of special AT-rich sequence-binding protein 2 (SATB2) has been approved associated with tumor progression, metastasis and unfavourable prognosis in various carcinomas. However, in oral squamous cell carcinoma (OSCC), both the expressive state and associated functions of SATB2's are still undefined. Here we show that, in clinical samples from a retrospective cohort of 58 OSCC patients, high expression of SATB2 is associated with poor prognosis of OSCC patients. In this study, we investigated SATB2 is highly expressed in OSCC tissues and cell lines, which can promote OSCC cells' proliferation, migration, invasion and tumor growth. According to sequencing results based on previous literature, we identified NOX4 is a bona fide downstream target of SATB2, when it was knockdown, OSCC's proliferation can be partially suppressed. Furthermore, NOX4 knockdown inhibits tumorigenicity, which can be rescued partially by ectopic expression of SATB2 in HNSCC cell line, and vice versa. Collectively, our findings not only indicate overexpression of SATB2 triggers the proliferative, migratory and invasive mechanisms which are important in the malignant phenotype of OSCC, but also identify NOX4 as the downstream gene for SATB2. These findings indicate that SATB2 may play a key role in OSCC tumorigenicity and may be a future target for the development of new therapeutic regimens.
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Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , NADPH Oxidase 4/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Estudos RetrospectivosRESUMO
INTRODUCTION: Delineating the margins of Oral squamous cell carcinoma (OSCC) is a critical step for optimaltumor resection. The aim of this study was to evaluate the accuracy of lesion surgical margin identification using autofluorescence visualization. MATERIALS AND METHODS: Thirty patients with OSCC were included in this study. For each lesion, the fluorescence loss boundary was determined using VELscope before ablative surgical resection (with a 1.5-2cm safety margin) was performed. A total of 126 samples were obtained from 30 surgical specimens, each containing the tissue from the fluorescence loss boundary to surgical margin. The status of each sample was determined by oral pathologists and the staining intensities of Ki-67, E-cadherin, and Vimentin at the fluorescence loss boundary and surgical margin were evaluated by immunohistochemistry. RESULTS: Fluorescence loss regions were identified in all patients. Of the 126 samples collected, HE staining identified 77 normal epithelia (61.1%), 26 mild dysplasia (20.6%), 17 severe dysplasia (13.4%) and 6 carcinomas in situ (4.9%). A significant correlation was found between the differentiation grade of tumor cells and the pathological status of the surgical marginal specimens (P<0.05). Forty-two of the 126 samples were randomly selected for further immunohistochemical staining. No significant differences were seen in Ki-67, E-cadherin, or Vimentin expression at the fluorescence loss boundary or surgical margin, however, the proteins' expression level was positively correlated with the degree of dysplasia (P<0.01). CONCLUSION: Autofluorescence visualization has potential as a simple surgical margin setting device for OSCC and may help delineate the superficial area of OSCC with acceptable accuracy. However, when considering the inherent limitations of this system, we suggest that the approach should only be applied under certain conditions, such as when dealing with superficial, well-differentiated lesions.