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1.
Exp Mol Med ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38825643

RESUMO

N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

2.
Adv Sci (Weinh) ; : e2401821, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738755

RESUMO

The demand for gas sensing systems that enable fast and precise gas recognition is growing rapidly. However, substantial challenges arise from the complex fabrication process of sensor arrays, time-consuming data transmission to an external processor, and high energy consumption in multi-stage data processing. In this study, a gas sensing system using on-chip annealing for fast and power-efficient gas detection is proposed. By utilizing a micro-heater embedded in the gas sensor, the sensing material of adjacent sensors in the same substrate can be easily varied without further fabrication steps. The response to oxidizing gas is constrained in metal oxide (MOX) sensing material with small grain sizes, as the depletion width of grain cannot extend beyond the grain size during the gas reaction. On the other hand, the response to reducing gases and humidity, which decrease the depletion width, is less affected by grain sizes. A readout circuit integrating a differential amplifier and dual FET-type gas sensors effectively emphasizes the response to oxidizing gases by canceling the response to reducing gases and humidity. The selective on-chip annealing method is applicable to various MOX sensing materials, demonstrating its potential for application in commercial fields due to its simplicity and expandability.

3.
Ann Lab Med ; 44(5): 426-436, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38529546

RESUMO

Background: Metformin, a drug prescribed for patients with type 2 diabetes, has potential efficacy in enhancing antitumor immunity; however, the detailed underlying mechanisms remain to be elucidated. Therefore, we aimed to identify the inhibitory molecular mechanisms of metformin on programmed death ligand 1 (PD-L1) expression in cancer cells and programmed death 1 (PD-1) expression in immune cells. Methods: We employed a luciferase reporter assay, quantitative real-time PCR, immunoblotting analysis, immunoprecipitation and ubiquitylation assays, and a natural killer (NK) cell-mediated tumor cell cytotoxicity assay. A mouse xenograft tumor model was used to evaluate the effect of metformin on tumor growth, followed by flow-cytometric analysis using tumor-derived single-cell suspensions. Results: Metformin decreased AKT-mediated ß-catenin S552 phosphorylation and subsequent ß-catenin transactivation in an adenosine monophosphate-activated protein kinase (AMPK) activation-dependent manner, resulting in reduced CD274 (encoding PD-L1) transcription in cancer cells. Tumor-derived soluble factors enhanced PD-1 protein stability in NK and T cells via dissociation of PD-1 from ubiquitin E3 ligases and reducing PD-1 polyubiquitylation. Metformin inhibited the tumor-derived soluble factor-reduced binding of PD-1 to E3 ligases and PD-1 polyubiquitylation, resulting in PD-1 protein downregulation in an AMPK activation-dependent manner. These inhibitory effects of metformin on both PD-L1 and PD-1 expression ameliorated cancer-reduced cytotoxic activity of immune cells in vitro and decreased tumor immune evasion and growth in vivo. Conclusions: Metformin blocks both PD-L1 and PD-1 within the tumor microenvironment. This study provided a mechanistic insight into the efficacy of metformin in improving immunotherapy in human cancer.


Assuntos
Antígeno B7-H1 , Células Matadoras Naturais , Metformina , Receptor de Morte Celular Programada 1 , beta Catenina , Metformina/farmacologia , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Animais , Linhagem Celular Tumoral , Camundongos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , beta Catenina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases Ativadas por AMP/metabolismo , Camundongos Endogâmicos BALB C , Fosforilação/efeitos dos fármacos , Camundongos Nus , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/imunologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Ubiquitinação/efeitos dos fármacos
4.
BMC Oral Health ; 24(1): 161, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302981

RESUMO

BACKGROUND: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset. METHODS: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network. RESULTS: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative [Formula: see text] score improvement rate of OPMD was 4.9%. CONCLUSIONS: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data.


Assuntos
Aprendizado Profundo , Neoplasias Bucais , Humanos , Inteligência Artificial , Currículo , Língua
5.
Sci Rep ; 14(1): 3397, 2024 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-38336901

RESUMO

Ridge resorption can result in insufficient bone volume for implant surgery, necessitating bone substitutes to restore the resorption area. Recent advances in computer-aided design and manufacturing enable the use of alloplastic bone graft materials with customizable compositions or shapes. This randomized study evaluated the clinical effectiveness of a customized three-dimensional (3D) printed alloplastic bone material. Sixty patients requiring guided bone regeneration for implant installation following tooth extraction due to alveolar bone resorption were recruited at two institutions. The participants were randomly allocated to either a group that received 3D-printed patient-customized bone graft material or a group that received conventional block bone graft material. Implant installation with bone harvesting was performed approximately 5 months after bone grafting. Histological and radiological assessments of the harvested bone area were performed. The experimental group had a significantly higher percent bone volume and a smaller tissue surface than the control group. Bone volume, bone surface, bone surface/volume ratio, bone surface density (bone surface/total volume), and bone mineral density did not differ significantly between groups. Patient-customized bone graft materials offer convenience and reduce patient discomfort. The findings suggest 3D-printed patient-customized bone graft materials could be used as an alternative for simpler bone grafting procedures.


Assuntos
Perda do Osso Alveolar , Substitutos Ósseos , Humanos , Transplante Ósseo/métodos , Estudos Prospectivos , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/cirurgia , Regeneração Óssea , Cerâmica
6.
J Hazard Mater ; 464: 132966, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-37976851

RESUMO

Exposure to ambient ultrafine particulate matter (UPM) causes respiratory disorders; however, the underlying molecular mechanisms remain unclear. In this study, we synthesized simulated UPM (sUPM) with controlled physicochemical properties using the spark-discharge method. Subsequently, we investigated the biological effects of sUPM using BEAS-2B human bronchial epithelial cells (HBECs) and a mouse intratracheal instillation model. High throughput RNA-sequencing and bioinformatics analyses revealed that dysregulation of the glycolytic metabolism is involved in the inhibited proliferation and survival of HBECs by sUPM treatment. Furthermore, signaling pathway and enzymatic analyses showed that the treatment of BEAS-2B cells with sUPM induces the inactivation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, also known as AKT), resulting in the downregulation of phosphofructokinase 2 (PFK2) S483 phosphorylation, PFK enzyme activity, and aerobic glycolysis in HBECs in an oxidative stress-independent manner. Additionally, intratracheal instillation of sUPM reduced the phosphorylation of ERK, AKT, and PFK2, decreased proliferation, and increased the apoptosis of bronchial epithelial cells in mice. The findings of this study imply that UPM induces pulmonary toxicity by disrupting aerobic glycolytic metabolism in lung epithelial cells, which can provide novel insights into the toxicity mechanisms of UPM and strategies to prevent their toxic effects.


Assuntos
Poluentes Atmosféricos , Material Particulado , Humanos , Animais , Camundongos , Material Particulado/análise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosforilação , Células Epiteliais , Glicólise , Fosfofrutoquinases/análise , Fosfofrutoquinases/metabolismo , Poluentes Atmosféricos/análise
7.
Sensors (Basel) ; 23(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38067818

RESUMO

Although several previous studies on laterality of upper limb motor control have reported functional differences, this conclusion has not been agreed upon. It may be conjectured that the inconsistent results were caused because upper limb motor control was observed in multi-joint tasks that could generate different inter-joint motor coordination for each arm. Resolving this, we employed a single wrist joint tracking task to reduce the effect of multi-joint dynamics and examined the differences between the dominant and non-dominant hands in terms of motor control. Specifically, we defined two sections to induce feedback (FB) and feedforward (FF) controls: the first section involved a visible target for FB control, and the other section involved an invisible target for FF control. We examined the differences in the position errors of the tracer and the target. Fourteen healthy participants performed the task. As a result, we found that during FB control, the dominant hand performed better than the non-dominant hand, while we did not observe significant differences in FF control. In other words, in a single-joint movement that is not under the influence of the multi-joint coordination, only FB control showed laterality and not FF control. Furthermore, we confirmed that the dominant hand outperformed the non-dominant hand in terms of responding to situations that required a change in control strategy.


Assuntos
Desempenho Psicomotor , Procedimentos Cirúrgicos Robóticos , Humanos , Movimento , Extremidade Superior , Lateralidade Funcional , Mãos
8.
J Exp Clin Cancer Res ; 42(1): 340, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38098117

RESUMO

BACKGROUND: Cancer cells undergo cellular adaptation through metabolic reprogramming to sustain survival and rapid growth under various stress conditions. However, how brain tumors modulate their metabolic flexibility in the naturally serine/glycine (S/G)-deficient brain microenvironment remain unknown. METHODS: We used a range of primary/stem-like and established glioblastoma (GBM) cell models in vitro and in vivo. To identify the regulatory mechanisms of S/G deprivation-induced metabolic flexibility, we employed high-throughput RNA-sequencing, transcriptomic analysis, metabolic flux analysis, metabolites analysis, chromatin immunoprecipitation (ChIP), luciferase reporter, nuclear fractionation, cycloheximide-chase, and glucose consumption. The clinical significances were analyzed in the genomic database (GSE4290) and in human GBM specimens. RESULTS: The high-throughput RNA-sequencing and transcriptomic analysis demonstrate that the de novo serine synthesis pathway (SSP) and glycolysis are highly activated in GBM cells under S/G deprivation conditions. Mechanistically, S/G deprivation rapidly induces reactive oxygen species (ROS)-mediated AMP-activated protein kinase (AMPK) activation and AMPK-dependent hypoxia-inducible factor (HIF)-1α stabilization and transactivation. Activated HIF-1α in turn promotes the expression of SSP enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). In addition, the HIF-1α-induced expression of glycolytic genes (GLUT1, GLUT3, HK2, and PFKFB2) promotes glucose uptake, glycolysis, and glycolytic flux to fuel SSP, leading to elevated de novo serine and glycine biosynthesis, NADPH/NADP+ ratio, and the proliferation and survival of GBM cells. Analyses of human GBM specimens reveal that the levels of overexpressed PHGDH, PSAT1, and PSPH are positively correlated with levels of AMPK T172 phosphorylation and HIF-1α expression and the poor prognosis of GBM patients. CONCLUSION: Our findings reveal that metabolic stress-enhanced glucose-derived de novo serine biosynthesis is a critical metabolic feature of GBM cells, and highlight the potential to target SSP for treating human GBM.


Assuntos
Proteínas Quinases Ativadas por AMP , Glioblastoma , Humanos , Glioblastoma/patologia , Serina , Glucose/metabolismo , Glicina , RNA , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Linhagem Celular Tumoral , Microambiente Tumoral , Fosfofrutoquinase-2
9.
Korean J Radiol ; 24(11): 1131-1141, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37899522

RESUMO

OBJECTIVE: Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. MATERIALS AND METHODS: This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). RESULTS: Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (ß = -216.21, P = 0.019) and insular cortex (ß = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. CONCLUSION: Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Masculino , Feminino , Humanos , Estudos Retrospectivos , Disfunção Cognitiva/diagnóstico por imagem , Encéfalo , Cognição , Doença de Alzheimer/diagnóstico por imagem , Ferro , Imageamento por Ressonância Magnética
10.
World J Surg Oncol ; 21(1): 253, 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37596637

RESUMO

BACKGROUND: Surgical management for chondrosarcoma of the temporomandibular joint (TMJ) is challenging due to the anatomical location involving the facial nerve and the functional joint. The purpose of this case series was to analyze the largest number of TMJ chondrosarcoma cases reported from a single institution and to review the literature about chondrosarcoma involving the TMJ. METHODS: Ten TMJ chondrosarcoma patients at Seoul National University Dental Hospital were included in this study. Radiographic features, surgical approaches, histopathologic subtypes, and treatment modalities were evaluated. All case reports of TMJ chondrosarcoma published in English from 1954 to 2021 were collected under PRISMA guidelines and comprehensively reviewed. RESULTS: The lesions were surgically resected in all 10 patients with efforts to preserve facial nerve function. Wide excision including margins of normal tissue was performed to ensure adequate resection margins. All TMJs were reconstructed with a metal condyle except one, which was reconstructed with vascularized costal bone. At last follow-up, all patients were still alive, and there had been no recurrence. Among 47 cases (patients from the literature and our cases), recurrence was specified in 43 and occurred in four (9.5%). CONCLUSIONS: For surgical management of TMJ chondrosarcoma, wide excision must consider preservation of the facial nerve. Reconstruction using a metal condyle prosthesis and a vascularized free flap is reliable. A more conservative surgical approach correlates with a favorable prognosis for facial nerve recovery. Nevertheless, wide excision is imperative to prevent tumor recurrence. In cases in which the glenoid fossa is unaffected by the tumor, it is deemed unnecessary to reconstruct the glenoid fossa within an oncological setting.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Retalhos de Tecido Biológico , Humanos , Recidiva Local de Neoplasia/cirurgia , Condrossarcoma/cirurgia , Margens de Excisão , Neoplasias Ósseas/cirurgia
11.
Adv Sci (Weinh) ; 10(27): e2206380, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37541303

RESUMO

Tumor cells often overexpress immune checkpoint proteins, including CD47, for immune evasion. However, whether or how oncogenic activation of receptor tyrosine kinases, which are crucial drivers in tumor development, regulates CD47 expression is unknown. Here, it is demonstrated that epidermal growth factor receptor (EGFR) activation induces CD47 expression by increasing the binding of c-Src to CD47, leading to c-Src-mediated CD47 Y288 phosphorylation. This phosphorylation inhibits the interaction between the ubiquitin E3 ligase TRIM21 and CD47, thereby abrogating TRIM21-mediated CD47 K99/102 polyubiquitylation and CD47 degradation. Knock-in expression of CD47 Y288F reduces CD47 expression, increases macrophage phagocytosis of tumor cells, and inhibits brain tumor growth in mice. In contrast, knock-in expression of CD47 K99/102R elicits the opposite effects compared to CD47 Y288F expression. Importantly, CD47-SIRPα blockade with an anti-CD47 antibody treatment significantly enhances EGFR-targeted cancer therapy. In addition, CD47 expression levels in human glioblastoma (GBM) specimens correlate with EGFR and c-Src activation and aggravation of human GBM. These findings elucidate a novel mechanism underlying CD47 upregulation in EGFR-activated tumor cells and underscore the role of the EGFR-c-Src-TRIM21-CD47 signaling axis in tumor evasion and the potential to improve the current cancer therapy with a combination of CD47 blockade with EGFR-targeted remedy.


Assuntos
Antígeno CD47 , Glioblastoma , Evasão Tumoral , Animais , Humanos , Camundongos , Antígeno CD47/metabolismo , Linhagem Celular Tumoral , Receptores ErbB , Glioblastoma/metabolismo , Fosforilação
12.
ACS Nano ; 17(18): 17790-17798, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37611120

RESUMO

Oxygen vacancies and adsorbed oxygen species on metal oxide surfaces play important roles in various fields. However, existing methods for manipulating surface oxygen require severe settings and are ineffective for repetitive manipulation. We present a method to manipulate the amount of surface oxygen by modifying the oxygen adsorption energy by electrically controlling the electron concentration of the metal oxide. The surface oxygen control ability of the method is verified using first-principles calculations based on density functional theory (DFT), X-ray photoelectron spectroscopy (XPS), and electrical resistance analysis. The presented method is implemented by fabricating oxide thin film transistors with embedded microheaters. The method can reconfigure the oxygen vacancies on the In2O3, SnO2, and IGZO surfaces so that specific chemisorption dominates. The method can selectively increase oxidizing (e.g., NO and NO) and reducing gas (e.g., H2S, NH3, and CO) reactions by electrically controlling the metal oxide surface to be oxygen vacancy-rich or adsorbed oxygen species-rich. The proposed method is applied to gas sensors and overcomes their existing limitations. The method makes the sensor insensitive to one gas (e.g., H2S) in mixed-gas environments (e.g., NO2+H2S) and provides a linear response (R2 = 0.998) to the target gas (e.g., NO2) concentration within 3 s. We believe that the proposed method is applicable to applications utilizing metal oxide surfaces.

13.
Redox Biol ; 65: 102810, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37478541

RESUMO

Exposure to ionizing radiation leads to oxidative damages in living cells. NADPH provides the indispensable reducing power to regenerate the reduced glutathione to maintain cellular redox equilibria. In mammalian cells, pentose phosphate pathway (PPP) is the major route to produce NADPH by using glycolytic intermediates, and the rate-limiting step of PPP is controlled by glucose-6-phosphate dehydrogenase (G6PD). Nevertheless, whether G6PD is timely co-opted under ionizing radiation to cope with oxidative stress remains elusive. Here we show that cellular G6PD activity is induced 30 min after ionizing radiation, while its protein expression is mostly unchanged. Mechanistically, casein kinase 2 (CK2) phosphorylates G6PD T145 under ionizing radiation, which consolidates the enzymatic activity of G6PD by facilitating G6PD binding with its substrate NADP+. Further, CK2-dependent G6PD T145 phosphorylation promotes NADPH production, decreases ROS level and supports cell proliferation under ionizing radiation. Our findings report a new anti-oxidative signaling route under ionizing radiation, by which CK2-mediated rapid activation of G6PD orchestrates NADPH synthesis to maintain redox homeostasis, thereby highlighting its potential value in the early treatment of ionizing radiation-induced injuries.


Assuntos
Caseína Quinase II , Glucosefosfato Desidrogenase , Animais , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , NADP/metabolismo , Fosforilação , Oxirredução , Radiação Ionizante , Homeostase , Via de Pentose Fosfato , Mamíferos/metabolismo
14.
J Craniofac Surg ; 34(8): 2297-2301, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37449576

RESUMO

The purpose of this study was to classify the skeletal phenotypes of adult patients with skeletal class III (C-III) malocclusion and unilateral or bilateral cleft lip and palate using principal component analysis and cluster analysis. The samples consisted of 81 adult C-III patients with cleft lip and palate (CLP) who underwent orthognathic surgery (OGS) or distraction osteogenesis (59 males and 22 females; 50 unilateral cleft lip and palate and 31 bilateral cleft lip and palate; mean age when lateral cephalograms were taken, 22.2±4.6 y). Thirteen angular and one ratio cephalometric variables were measured. Using 4 representative variables obtained from principal component analysis (SNA, SNB, Gonial angle, and Bjork sum), K-means cluster analysis was performed to classify the phenotypes. Then, statistical analysis was conducted to characterize the differences in the variables among the clusters. Five clusters were obtained from 3 groups: severely retrusive maxilla and moderately retrusive mandible group: cluster-1 (23.5%, severely hyperdivergent pattern), cluster-4 (27.2%, moderately hyperdivergent pattern), and cluster-5 (11.1%, normodivergent pattern); moderately retrusive maxilla and normal mandible group: cluster-2 (30.9%, normodivergent pattern); normal maxilla and moderately protrusive mandible group: cluster-3 (7.4%, normodivergent pattern). Although skeletal phenotypes were diverse, distribution of sex and cleft type did not differ among 5 clusters ( P >0.05). Sixty-two percent of cleft patients showed a severely retrusive maxilla and moderately retrusive mandible (cluster-1, cluster-4, and cluster-5), which indicated that these are the main cause of skeletal C-III malocclusion in CLP patients who were treated with OGS. Therefore, it is necessary to consider presurgical orthodontic treatment and surgical planning based on the skeletal phenotypes of CLP patients.


Assuntos
Fenda Labial , Fissura Palatina , Má Oclusão Classe III de Angle , Masculino , Feminino , Humanos , Adulto , Fenda Labial/cirurgia , Fenda Labial/complicações , Fissura Palatina/cirurgia , Fissura Palatina/complicações , Análise de Componente Principal , Má Oclusão Classe III de Angle/cirurgia , Má Oclusão Classe III de Angle/etiologia , Mandíbula/cirurgia , Maxila/cirurgia , Cefalometria
15.
Cancers (Basel) ; 15(11)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37296861

RESUMO

The association between oral microbiota and cancer development has been a topic of intense research in recent years, with compelling evidence suggesting that the oral microbiome may play a significant role in cancer initiation and progression. However, the causal connections between the two remain a subject of debate, and the underlying mechanisms are not fully understood. In this case-control study, we aimed to identify common oral microbiota associated with several cancer types and investigate the potential mechanisms that may trigger immune responses and initiate cancer upon cytokine secretion. Saliva and blood samples were collected from 309 adult cancer patients and 745 healthy controls to analyze the oral microbiome and the mechanisms involved in cancer initiation. Machine learning techniques revealed that six bacterial genera were associated with cancer. The abundance of Leuconostoc, Streptococcus, Abiotrophia, and Prevotella was reduced in the cancer group, while abundance of Haemophilus and Neisseria enhanced. G protein-coupled receptor kinase, H+-transporting ATPase, and futalosine hydrolase were found significantly enriched in the cancer group. Total short-chain fatty acid (SCFAs) concentrations and free fatty acid receptor 2 (FFAR2) expression levels were greater in the control group when compared with the cancer group, while serum tumor necrosis factor alpha induced protein 8 (TNFAIP8), interleukin-6 (IL6), and signal transducer and activator of transcription 3 (STAT3) levels were higher in the cancer group when compared with the control group. These results suggested that the alterations in the composition of oral microbiota can contribute to a reduction in SCFAs and FFAR2 expression that may initiate an inflammatory response through the upregulation of TNFAIP8 and the IL-6/STAT3 pathway, which could ultimately increase the risk of cancer onset.

16.
Biomed Eng Lett ; 13(2): 235-243, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37124111

RESUMO

This study evaluated the biomechanical microenvironmental stimulating effect of pulsed electromagnetic field (PEMF) on the regeneration of crush-injured rat sciatic nerve, when combined with bone marrow mesenchymal stem cells (BMSCs) and recombinant human nerve growth factor (rhNGF-ß), in the form of an adenoviral vector-mediated NGF. Sprague-Dawley rats were equally distributed into six groups; PBS, BMSC, NGF-Ad + BMSC, PEMF + PBS, PEMF + BMSC and PEMF + NGF-Ad + BMSC. The PBS group received PBS (volume: 10µL/rat), the BMSC group with BMSCs (1 × 106 cell/10 µL/rat) and NGF-Ad group with the rhNGF-ß Ad infected BMSCs (1 × 106 cell/10 µL/rat) immediate after right sciatic nerve crush injury. The PEMF groups were exposed to PEMF of 1mT, 50 Hz, 1 h/day. The rats were observed for 3 weeks. PEMF alone did not showed the positive effect compared with negative control group. The groups transplanted with BMSCs showed higher axonal regeneration compared with the groups without transplantation of the cells whether BMSC was infected with NGF-Ad or not and whether the animals received PEMF. PEMF + NGF-Ad + BMSC group showed the significantly highest number of axons than the other groups. Functionally, all groups showed marked improvement at 3 weeks postoperatively although the difference was not statistically significant among the groups. PEMF showed the positive effect when combined with BMSC and NGF-ad in aspect of number of axons. Therefore, combining the microenvironment stimulation methods of PEMF and conventional methods such as transplantation of stem cells and growth factor could be considered for the regeneration methods in the nerve damage.

17.
ACS Appl Mater Interfaces ; 15(18): 22651-22661, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37115020

RESUMO

Low-power metal oxide (MOX)-based gas sensors are widely applied in edge devices. To reduce power consumption, nanostructured MOX-based sensors that detect gas at low temperatures have been reported. However, the fabrication process of these sensors is difficult for mass production, and these sensors are lack uniformity and reliability. On the other hand, MOX film-based gas sensors have been commercialized but operate at high temperatures and exhibit low sensitivity. Herein, commercially advantageous highly sensitive, film-based indium oxide sensors operating at low temperatures are reported. Ar and O2 gases are simultaneously injected during the sputtering process to form a hydroxy-rich-surface In2O3 film. Conventional indium oxide (In2O3) films (A0) and hydroxy-rich indium oxide films (A1) are compared using several analytical techniques. A1 exhibits a work function of 4.92 eV, larger than that of A0 (4.42 eV). A1 exhibits a Debye length 3.7 times longer than that of A0. A1 is advantageous for gas sensing when using field effect transistors (FETs) and resistors as transducers. Because of the hydroxy groups present on the surface of A1, A1 can react with NO2 gas at a lower temperature (∼100 °C) than A0 (180 °C). Operando diffuse reflectance infrared Fourier transform spectrometry (DRIFTS) shows that NO2 gas is adsorbed to A1 as nitrite (NO2-) at 100 °C and nitrite and nitrate (NO3-) at 200 °C. After NO2 is adsorbed as nitrate, the sensitivity of the A1 sensor decreases and its low-temperature operability is compromised. On the other hand, when NO2 is adsorbed only as nitrite, the performance of the sensor is maintained. The reliable hydroxy-rich FET-type gas sensor shows the best performance compared to that of the existing film-based NO2 gas sensors, with a 2460% response to 500 ppb NO2 gas at a power consumption of 1.03 mW.

18.
Neuroimage ; 273: 120058, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36997135

RESUMO

The in-vivo profiling of iron and myelin across cortical depths and underlying white matter has important implications for advancing knowledge about their roles in brain development and degeneration. Here, we utilize χ-separation, a recently-proposed advanced susceptibility mapping that creates positive (χpos) and negative (χneg) susceptibility maps, to generate the depth-wise profiles of χpos and χneg as surrogate biomarkers for iron and myelin, respectively. Two regional sulcal fundi of precentral and middle frontal areas are profiled and compared with findings from previous studies. The results show that the χpos profiles peak at superificial white matter (SWM), which is an area beneath cortical gray matter known to have the highest accumulation of iron within the cortex and white matter. On the other hand, the χneg profiles increase in SWM toward deeper white matter. These characteristics in the two profiles are in agreement with histological findings of iron and myelin. Furthermore, the χneg profiles report regional differences that agree with well-known distributions of myelin concentration. When the two profiles are compared with those of QSM and R2*, different shapes and peak locations are observed. This preliminary study offers an insight into one of the possible applications of χ-separation for exploring microstructural information of the human brain, as well as clinical applications in monitoring changes of iron and myelin in related diseases.


Assuntos
Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Bainha de Mielina , Ferro , Imageamento por Ressonância Magnética/métodos , Encéfalo , Substância Cinzenta/diagnóstico por imagem
19.
J Craniofac Surg ; 34(3): e314-e319, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939920

RESUMO

The purpose of this study was to classify and characterize facial asymmetry (FA) phenotypes in adult patients with unilateral cleft lip and palate (UCLP) and skeletal class III malocclusion. The samples comprised 52 adult UCLP patients (36 men and 16 women; mean age, 22.43 y) who had undergone orthognathic surgery for correction of class III malocclusion. After measurement of 22 cephalometric parameters in posteroanterior cephalograms taken 1 month before orthognathic surgery, principal component analysis was performed to obtain 5 representative parameters [deviation (mm) of ANS (ANS-dev), maxillary central incisor contact point (Mx1-dev), and menton (Me-dev); cant (degree) of the maxillary anterior occlusal plane (MxAntOP-cant) and mandibular border (MnBorder-cant)]. K-means cluster analysis was conducted using these representative parameters. The differences in cephalometric parameters among the clusters were statistically analyzed. The FA phenotypes were classified into 4 types: No-cant-and-No-deviation type (cluster-4, n=16, 30.8%); MxMn-cant-MxMn-dev to the cleft-side type (cluster-3, n=4, 7.7%); Mx-cant-Mn-shift to the cleft-side type (cluster-2, n=15, 28.8%); and Mn-cant-Mn-dev to the noncleft-side type (cluster-1, n=17, 32.7%). Asymmetry in the maxilla and/or mandible were observed in 70% of patients. One third of patients (cluster-2 and cluster-3; sum, 36.5%) exhibited significant cant of MxAntOP induced by cleft and cant or shift of the mandible to the cleft side. Another one third of patients (cluster-1, 32.7%) demonstrated significant deviation and cant of the mandible to the noncleft-side despite cleft in the maxilla. This FA phenotype classification might be a basic guideline for diagnosis and treatment planning for UCLP patients.


Assuntos
Fenda Labial , Fissura Palatina , Má Oclusão Classe III de Angle , Feminino , Humanos , Fenda Labial/cirurgia , Assimetria Facial/cirurgia , Fissura Palatina/cirurgia , Análise de Componente Principal , Estudos Retrospectivos , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Maxila/cirurgia , Cefalometria
20.
Discov Nano ; 18(1): 24, 2023 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-36829069

RESUMO

The need for high-performance gas sensors is driven by concerns over indoor and outdoor air quality, and industrial gas leaks. Due to their structural diversity, vast surface area, and geometric tunability, metal oxides show significant potential for the development of gas sensing systems. Despite the fact that several previous reports have successfully acquired a suitable response to various types of target gases, it remains difficult to maintain the reliability of metal oxide-based gas sensors. In particular, the degradation of the sensor platform under repetitive operation, such as off-state stress (OSS) causes significant reliability issues. We investigate the impact of OSS on the gas sensing performances, including response, low-frequency noise, and signal-to-noise ratio of horizontal floating-gate field-effect-transistor (FET)-type gas sensors. The 1/f noise is increased after the OSS is applied to the sensor because the gate oxide is damaged by hot holes. Therefore, the SNR of the sensor is degraded by the OSS. We applied a self-curing method based on a PN-junction forward current at the body-drain junction to repair the damaged gate oxide and improve the reliability of the sensor. It has been demonstrated that the SNR degradation caused by the OSS can be successfully recovered by the self-curing method.

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