Search

As a typical hard but brittle material, Si tends to fracture abruptly at a stress well below its theoretical strength, even if the tested volume goes down to submicron scale, at which materials are usually nearly free of flaws or extended defects. Here, via the thermal–oxidation–mediated healing of the surface that is the preferred site for cracks or dislocations initiation, the premature fracture can be effectively inhibited and the over 50% homogeneous plastic strain with the near‐theoretical strength (twice the value of the unhealed counterpart) are united in submicron‐sized Si particles. In situ transmission electron microscope observations and atomistic simulations elucidate the confinement effect from the passivated and smoothened thermal oxide, which retards the dislocation nucleation and transforms the dominant deformation mechanism from partial dislocation to the more mobile full dislocation. This work demonstrates an effective and feasible surface engineering pathway to optimize the mechanical properties of Si at small scales. [ABSTRACT FROM AUTHOR]

Aim: Human stem cells from the apical papilla (SCAPs) are an appealing stem cell source for tissue regeneration engineering. Circular RNAs (circRNAs) are known to exert pivotal regulatory functions in various cell differentiation processes, including osteogenesis of mesenchymal stem cells. However, few studies have shown the potential mechanism of circRNAs in the odonto/osteogenic differentiation of SCAPs. Herein, we identified a novel circRNA, circ‐ZNF236 (hsa_circ_0000857) and found that it was remarkably upregulated during the SCAPs committed differentiation. Thus, in this study, we showed the significance of circ‐ZNF236 in the odonto/osteogenic differentiation of SCAPs and its underlying regulatory mechanisms. Methodology: The circular structure of circ‐ZNF236 was identified via Sanger sequencing, amplification of convergent and divergent primers. The proliferation of SCAPs was detected by CCK‐8, flow cytometry analysis and EdU incorporation assay. Western blotting, qRT‐PCR, Alkaline phosphatase (ALP) and Alizarin red staining (ARS) were performed to explore the regulatory effect of circ‐ZNF236/miR‐218‐5p/LGR4 axis in the odonto/osteogenic differentiation of SCAPs in vitro. Fluorescence in situ hybridization, as well as dual‐luciferase reporting assays, revealed that circ‐ZNF236 binds to miR‐218‐5p. Transmission electron microscopy (TEM) and mRFP‐GFP‐LC3 lentivirus were performed to detect the activation of autophagy. Results: Circ‐ZNF236 was identified as a highly stable circRNA with a covalent closed loop structure. Circ‐ZNF236 had no detectable influence on cell proliferation but positively regulated SCAPs odonto/osteogenic differentiation. Furthermore, circ‐ZNF236 was confirmed as a sponge of miR‐218‐5p in SCAPs, while miR‐218‐5p targets LGR4 mRNA at its 3′‐UTR. Subsequent rescue experiments revealed that circ‐ZNF236 regulates odonto/osteogenic differentiation by miR‐218‐5p/LGR4 in SCAPs. Importantly, circ‐ZNF236 activated autophagy, and the activation of autophagy strengthened the committed differentiation capability of SCAPs. Subsequently, in vivo experiments showed that SCAPs overexpressing circ‐ZNF236 promoted bone formation in a rat skull defect model. Conclusions: Circ‐ZNF236 could activate autophagy through increasing LGR4 expression, thus positively regulating SCAPs odonto/osteogenic differentiation. Our findings suggested that circ‐ZNF236 might represent a novel therapeutic target to prompt the odonto/osteogenic differentiation of SCAPs. [ABSTRACT FROM AUTHOR]

Aim: Recently, miR‐27b‐5p was shown to be abundantly expressed in extracellular vehicles (EVs) from the inflammatory microenvironment. This study determined the role of miR‐27b‐5p in regulating osteogenic and odontogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs) and further examined the regulatory mechanism of bone morphogenetic protein receptor type‐1A (BMPR1A). Methodology: Characteristics of SHEDs and SHEDs‐EVs derived from SHEDs were evaluated respectively. The expression of miR‐27b‐5p in SHEDs and EVs was detected during osteo‐induction. Mechanically, SHEDs were treated with miR‐27b‐5p mimics or an inhibitor, and the osteogenic/odontogenic differentiation and proliferation were assessed. Bioinformatic analysis and luciferase reporter were utilized for target gene prediction and verification. Finally, BMPR1A‐overexpressed plasmids were transfected into SHEDs to investigate the participation of the BMPR1A/SMAD4 pathway. Data were analysed using Student's t‐test, one‐way analysis of variance and Chi‐square test. Results: MiR‐27b‐5p was expressed in both SHEDs and EVs and was significantly increased at the initial stage of differentiation and then decreased in a time‐dependent manner (p <.01). Upregulation of miR‐27b‐5p significantly suppressed osteogenic/odontogenic differentiation of SHEDs and inhibited proliferation (p <.05), whereas inhibition of miR‐27b‐5p enhanced the differentiation (p <.05). Dual‐luciferase reporter assay and pull‐down assay confirmed the binding site between miR‐27b‐5p and BMPR1A (p <.05). The overexpression of BMPR1A rescued the effect of miR‐27b‐5p, while contributed to the decrease of pluripotency (p <.05). Additionally, miR‐27b‐5p maintained pluripotency in BMPR1A‐overexpressed SHEDs (p <.05). Conclusions: MiR‐27b‐5p in SHEDs/EVs was inversely associated with differentiation and suppressed the osteogenic and odontogenic differentiation of SHEDs and maintained the pluripotency of SHEDs partly by shuttering BMPR1A‐targeting BMP signalling. Theoretically, inhibition of miR‐27b‐5p represents a potential strategy to promote osteanagenesis and dentinogenesis. However, miR‐27b‐5p capsuled EVs might maintain cell pluripotency and self‐renewal for non‐cell‐targeted therapy. [ABSTRACT FROM AUTHOR]

Cisplatin resistance poses a substantial hurdle in effectively treating head and neck squamous cell carcinoma (HNSCC). Utilizing multiple tumor models and examining an internal HNSCC cohort, squalene epoxidase (SQLE) is pinpointed as a key driver of chemoresistance and tumorigenesis, operating through a cholesterol‐dependent pathway. Comprehensive transcriptomic analysis reveals that SQLE is essential for maintaining c‐Myc transcriptional activity by stabilizing the c‐Myc protein and averting its ubiquitin‐mediated degradation. Mechanistic investigation demonstrates that SQLE inhibition diminishes Akt's binding affinity to lipid rafts via a cholesterol‐dependent process, subsequently deactivating lipid raft‐localized Akt, reducing GSK‐3β phosphorylation at S9, and increasing c‐Myc phosphorylation at T58, ultimately leading to c‐Myc destabilization. Importantly, employing an Sqle conditional knockout mouse model, SQLE's critical role in HNSCC initiation and progression is established. The preclinical findings demonstrate the potent synergistic effects of combining terbinafine and cisplatin in arresting tumor growth. These discoveries not only provide novel insights into the underlying mechanisms of SQLE‐mediated cisplatin resistance and tumorigenesis in HNSCC but also propose a promising therapeutic avenue for HNSCC patients unresponsive to conventional cisplatin‐based chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the regulatory effect of hypoxia on human periodontal ligament stem cells (PDLSCs) through RNA sequencing (RNA SEQ). Human PDLSCs were cultured in normoxia (20% O2) or hypoxia (2% O2). Material and Methods: Total RNA was extracted and sequenced. The expression profiles of circRNAs, lncRNAs, and miRNAs were determined, and the lncRNA/circRNA‐miRNA‐mRNA networks were analyzed. Results: In total, 15 miRNAs, 449 lncRNAs, and 53 circRNAs were differentially expressed. Among them, 21 circRNAs, 262 lncRNAs, 5 miRNAs, and 5 mRNAs were selected to construct competing endogenous RNA (ceRNA) networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to explore potential related pathways and regulatory functions. Several ceRNA axes (lncRNA‐FTX/circRNA‐FAT1‐hsa‐miR‐4781‐3p‐SMAD5 and circRNA LPAR1‐hsa‐miR‐342‐3p‐ADAR) may provide a theoretical basis on the study of osteogenic differentiation of PDLSCs under hypoxia. Conclusion: This study revealed that the expression profiles of circRNAs, lncRNAs, and miRNAs had changed significantly in PDLSCs cultured in 2% O2; specific circRNAs/lncRNAs may play a competitive role in the differentiation of PDLSCs. [ABSTRACT FROM AUTHOR]

Conflicting evidence exists regarding the effectiveness of magnesium supplementation during pregnancy in gestational diabetes mellitus (GDM) patients. This meta‐analysis examines the effect of magnesium on glycemic indices and metabolic status in GDM. We searched databases for randomized controlled trials (RCTs) conducted, and after applying inclusion and exclusion criteria, a total of four RCTs were considered eligible for the analysis. Outcome parameters included markers for glycemic control and metabolic status. A total of four RCTs with 198 participants (control = 99; magnesium supplemented = 99) were selected for the analysis. Magnesium supplementation resulted in a significant reduction in markers of glycemic control—fasting plasma glucose (standard mean difference (μ^) = −0.83; 95% CI: [−1.13, –0.54]; p‐value <.0001), and insulin levels (μ^ = −0.95; 95% CI: [−1.38, −0.52]; p‐value <.0001). Also, Mg intake resulted in altered oxidative stress markers TAC (μ^ = 1.09; 95% CI: [0.10, 2.07]; p‐value =.03) of the pregnant women. No significant effect on GSH and CRP levels was observed. This study provides evidence of the positive effects of magnesium intervention on insulin sensitivity and oxidative stress in GDM patients. [ABSTRACT FROM AUTHOR]

Artificial intelligence approaches to analyze pathological images (pathomic) for outcome prediction have not been sufficiently considered in the field of pituitary research. A total of 5,504 hematoxylin & eosin‐stained pathology image tiles from 58 acromegalic patients with a good or poor outcome were integrated with other clinical and genetic information to train a low‐rank fusion convolutional neural network (LFCNN). The model was externally validated in 1,536 patches from an external cohort. The primary outcome was the time to the first endocrine remission after stereotactic radiosurgery (SRS). The median time of initial endocrine remission was 43 months (interquartile range [IQR]: 13–60 months) after SRS, and the 24‐month initial cumulative remission rate was 57.9% (IQR: 46.4–72.3%). The patient‐wise accuracy of the LFCNN model in predicting the primary outcome was 92.9% in the internal test dataset, and the sensitivity and specificity were 87.5 and 100.0%, respectively. The LFCNN model was a strong predictor of initial cumulative remission in the training cohort (hazard ratio [HR] 9.58, 95% confidence interval [CI] 3.89–23.59; p < 0.001) and was higher than that of established prognostic markers. The predictive value of the LFCNN model was further validated in an external cohort (HR 9.06, 95% CI 1.14–72.25; p = 0.012). In this proof‐of‐concept study, clinically and genetically useful prognostic markers were integrated with digital images to predict endocrine outcomes after SRS in patients with active acromegaly. The model considerably outperformed established prognostic markers and can potentially be used by clinicians to improve decision‐making regarding adjuvant treatment choices. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Surgeons face challenges in intraoperatively defining margin of brain tumors due to its infiltrative nature. Extracellular acidosis caused by metabolic reprogramming of cancer cells is a reliable marker for tumor infiltrative regions. Although the acidic margin‐guided surgery shows promise in improving surgical prognosis, its clinical transition is delayed by having the exogenous probes approved by the drug supervision authority. Here, an intelligent surface‐enhanced Raman scattering (SERS) navigation system delineating glioma acidic margins without administration of exogenous probes is reported. With assistance of this system, the metabolites at the tumor cutting edges can be nondestructively transferred within a water droplet to a SERS chip with pH sensitivity. Homemade deep learning model automatically processes the Raman spectra collected from the SERS chip and delineates the pH map of tumor resection bed with increased speed. Acidity correlated cancer cell density and proliferation level are demonstrated in tumor cutting edges of animal models and excised tissues from glioma patients. The overall survival of animal models post the SERS system guided surgery is significantly increased in comparison to the conventional strategy used in clinical practice. This SERS system holds the promise in accelerating clinical transition of acidic margin‐guided surgery for solid tumors with infiltrative nature. [ABSTRACT FROM AUTHOR]

An extreme warm winter (ranked first during the past 30‐years) occurred in Shanghai in 2019, accompanied with an extreme rainy winter (ranked thirdly in the same period). An observational diagnosis shows that the extreme warm and rainy winter arose from southerly anomalies associated with an anticyclone east of Shanghai. The cause of the anticyclone was attributed to V‐shaped upper‐tropospheric Rossby wave activity fluxes, originated from the North Atlantic and tropical Indian Ocean. Numerical model experiments indicate that the anomalous heat source in the tropical Indian Ocean played a dominant role (~65%) in causing the local anomalous circulation, while the heating in North Atlantic also played a role (~35%). A further analysis of the past 30 year data revealed that an extreme warm winter in the past did not coincide with an extreme wet winter. While the warm winter composite shows a large‐scale anticyclone anomaly over Central and East Asia, the rainy winter composite exhibits a circulation dipole pattern with an anomalous cyclone (anticyclone) west (east) of Shanghai. Numerical experiments confirm that the former was forced by the combined effect of precipitation anomalies over the North Atlantic and tropical Indian Ocean (IO) and Maritime Continent (MC) through Rossby wave energy dispersion, whereas the latter was caused by a dipole heating pattern over the tropical IO/MC sector. [ABSTRACT FROM AUTHOR]

Objective: The conditioned medium of calcined tooth powder (CTP‐CM) is a type of biomimetic mineralized material and well contributing to bone healing and bone formation in vivo. However, little is known about the effect of CTP‐CM on human periodontal ligament stem cells (hPDLSCs) as well as the underlying mechanisms. Methods: ALP activity assay was conducted to select the concentration with the highest ALP level, which was used for the following experiments. Cell proliferation was measured by cell counting kit‐8 assay and flow cytometry analysis. Expression levels of osteogenic markers in CTP‐CM‐induced hPDLSCs were evaluated with real‐time quantitative reverse transcription polymerase chain reaction (qRT‐PCR), immunofluorescence staining, and Western blot. Mineralization of CTP‐CM‐induced hPDLSCs was evaluated by alizarin red staining. Furthermore, the involvement of NF‐κB pathway was examined by immunofluorescence staining and Western blot. Results: 20 μg/ml was selected for the further experiments. Functional studies demonstrated that CTP‐CM exerted almost no influence on the proliferation of hPDLSCs and CTP‐CM increased the osteogenic differentiation of hPDLSCs. Mechanistically, CTP‐CM leads to activation of NF‐κB signaling pathway. When treated with BMS345541, the osteogenic differentiation of CTP‐CM‐treated hPDLSCs was significantly attenuated. Conclusion: CTP‐CM can promote the osteogenic differentiation of hPDLSCs via activating NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Purpose: Early identification of ischemic stroke lesion regions plays a vital role in its treatments like thrombolytic therapy and patients' recovery. Noncontrast computed tomography (ncCT) is the most widespread imaging modality in emergency departments. Unfortunately, it is extremely hard to distinguish the lesion from healthy tissue during the hyper‐acute phase of stroke. In this paper, a two‐stage convolutional neural network‐based method was proposed to identify the invisible ischemic stroke from ncCT. Methods: In order to combine the global and local information of images effectively, a cascaded structure with two coordinated networks was used to detect the suspicious stroke regions on the whole and optimize the detailed localization. In the first stage, an end‐to‐end U‐net with adaptive threshold was proposed to integrate global position, symmetry and gray texture information to detect the suspicious regions. After reducing the interference from most normal regions, a ResNet‐based patch classification network was used to eliminate some false positive samples on suspicious regions by mining deeper image features, contributing to a more precise localization of stroke. Finally, a MAP model was used to optimize the result by combining the classification results of each patch with their spatial constraint information. Results: Three independent experiments, that is, training and testing on dataset from one hospital, on the combination of two, and on the two respectively, were performed on a total of 277 cases from two hospitals to validate the proposed model, The proposed method achieved identification accuracy of 91.89%, 87.21%, and 85.71% in the three experiments, and the final localization accuracy in terms of precise localization of stroke were 82.35%, 83.02%, and 81.40%, respectively, which indicated the robustness and clinical values of the method. Conclusions: There are some deep image feature differences between stroke region and normal region on ncCT images. The proposed two‐stage convolutional neural network model can well seize these features and use them to effectively identify and locate stroke. [ABSTRACT FROM AUTHOR]

Hyperoside, as an active compound, widely exists in a large number of Chinese herbal medicines and has been reported to possess anti‐inflammatory and diuretic properties. However, the effects and underlying mechanisms of hyperoside on periodontitis have not been previously reported. In this study, we found that hyperoside ameliorates symptoms of periodontitis in a rat model, with improvements in alveolar bone resorption, relief of inflammatory infiltration, increase in orderly arrangement of collagen fibers and increase of osteogenic differentiation. In addition, hyperoside promoted proliferation, up‐regulated EdU‐positive cells, decreased cell‐cycle distribution and increased the protein expression of Ki67 and PCNA in rat bone mesenchymal stem cells (rBMSCs), as revealed by Cell Counting Kit‐8, EdU, flow cytometry and western blot analysis. Moreover, hyperoside significantly promoted osteogenic differentiation, as shown by quantitative RT‐PCR, western blot and alizarin red staining assays. Furthermore, hyperoside activated the nuclear factor‐κB (NF‐κB) signaling pathway in rBMSCs, similar to the results observed in vivo. Finally, BMS345541, an inhibitor of the NF‐κB signaling pathway, could reverse the effects of hyperoside on the biological functions in rBMSCs. In conclusion, our results suggest that hyperoside has potential therapeutic properties against periodontitis via promotion of proliferation and osteogenic differentiation of rBMSCs via activation of the NF‐κB signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Parathyroid hormone (PTH) is a main systemic mediator of calcium and phosphate homeostasis in the bone. Dental pulp stem cells (DPSCs) have been extensively studied in the regeneration of bone and tooth tissues. This paper aims to uncover the influences of PTH on the proliferative ability and osteo/odontogenic differentiation of DPSCs, as well as the underlying mechanisms. Materials and Methods: The optimal concentration of PTH on DPSCs was determined by alkaline phosphatase (ALP) activity assay, ALP staining and western blot analysis. Proliferative ability and cell cycle distribution of DPSCs were analyzed by Cell counting kit‐8, 5‐ethynyl‐20‐deoxyuridine assay, and flow cytometry. Osteo/odontogenic capacity of DPSCs was evaluated and finally, the involvement of mitogen‐activated protein kinase (MAPK) pathway was assessed. Results: Purified DPSCs were obtained by enzymatic digestion, which presented a typical fibroblast‐like morphology. 10−9 mol/L PTH was concerned as the optimal concentration for DPSCs induction. 10−9 mol/L PTH treatment did not change the proliferative rate of DPSCs (p > .05). Relative expressions of DSPP/DSPP, RUNX2/RUNX2, OSX/OSX, and ALP/ALP were upregulated in PTH‐treated DPSCs relative to control group. Particularly, their mRNA/protein levels at Day 7 were markedly higher relative to those at Day 3 (p < .05 or p < .01). Mineralized nodules were formed after PTH induction, and calcium content increased by cetylpyridinium chloride quantitative analysis. Mechanistically, the protein levels of p‐ERK and p‐P38 significantly increased after PTH treatment, and the inhibitors targeting MAPK were identified that weakened the effects of PTH on the committed differentiation of DPSCs. Conclusions: PTH enhances the osteo/odontogenic differentiation capacity of DPSCs via ERK and P38 signaling pathways. [ABSTRACT FROM AUTHOR]

Fluoride (sodium fluoride) is thought to be essential in the development of tooth, and research shows that fluoride can modulate the differentiation of dental stem cells. However, the effects of fluoride on the committed differentiation of stem cells from apical papilla (SCAPs) and the underlying mechanisms remain unclear. Here, SCAPs were isolated from healthy extracted human third molars with immature roots and then were cultured with NaF conditioned media. Cell Counting Kit‐8, EdU staining, and flow cytometry were performed to detected the proliferation activity. Alkaline phosphatase (ALP) activity, Alizarin Red staining, Western blot assay, and real‐time reverse‐transcription polymerase chain reaction were applied to assess the osteo/odontogenic differentiation NaF‐treated SCAPs. Western blot assay and transmission electron microscope were used to evaluate the autophagy involved in the differentiation of SCAPs. ALP activity, ALP protein, and messenger RNA (mRNA) expression showed that 0.5 mM was the optimal concentration for the induction of SCAPs by NaF. 0.5 mM NaF‐treated SCAPs induced more mineralized nodules as compared with untreated cells. Moreover, the osteo/odontogenic markers (RUNX2, OSX, DSP, and OCN) in mRNA levels were upregulated while the protein levels of these markers increased considerably in 0.5 mM NaF‐treated SCAPs. Furthermore, the autophagy‐related proteins (LC3, ATG5, and Beclin1) increased in NaF‐treated SCAPs, and the osteo/odontogenic makers significantly decreased while silencing ATG5 to block autophagy. In all, sodium fluoride can regulate the osteo/odontogenic differentiation of SCAPs by modulating autophagy. [ABSTRACT FROM AUTHOR]

Purpose: Accurately predicting outcome (i.e., overall survival (OS) time) for higher grade glioma (HGG) has great clinical value and would provide optimized guidelines for treatment planning. Radiomics focuses on revealing underlying pathophysiological information in biomedical images for disease analysis and demonstrates promising prognostic clinical performance. In this paper, we propose a novel sparse representation‐based radiomics framework to predict if HGG patients would have long or short OS time. Methods: First, taking advantages of the scale invariant feature transform (SIFT) feature in image characterizing, we developed a sparse representation‐based method to convert a local SIFT descriptor into a global tumor feature. Next, because preserving sample structure is beneficial for feature selection, we proposed a locality preserving projection and sparse representation‐combined feature selection method to select more discriminative features for tumor classification. Finally, we employed a multifeature collaborative sparse representation classification to combine the information of multimodal images to classify OS time. Results: Three experiments were performed on the two datasets provided by different institutions. Specifically, the proposed model was trained and independently tested on dataset 1 (135 subjects), on dataset 2 (86 subjects), and on the combination of dataset 1 and dataset 2, respectively. Experimental results demonstrated that the proposed method achieved encouraging prediction performance, exhibiting a testing accuracy of 93.33% on dataset 1 (one modality), 92.31% on dataset 2 (two modalities), and 87.93% on the combined dataset (one modality). Conclusions: The sparse representation theory provides reasonable solutions to feature extraction, feature selection, and classification for radiomics. This study provides a promising tool to enhance the prediction performance of HGG patient's outcome. [ABSTRACT FROM AUTHOR]

Purpose: Due to the low contrast, blurry boundaries, and large amount of shadows in breast ultrasound (BUS) images, automatic tumor segmentation remains a challenging task. Deep learning provides a solution to this problem, since it can effectively extract representative features from lesions and the background in BUS images. Methods: A novel automatic tumor segmentation method is proposed by combining a dilated fully convolutional network (DFCN) with a phase‐based active contour (PBAC) model. The DFCN is an improved fully convolutional neural network with dilated convolution in deeper layers, fewer parameters, and batch normalization techniques; and has a large receptive field that can separate tumors from background. The predictions made by the DFCN are relatively rough due to blurry boundaries and variations in tumor sizes; thus, the PBAC model, which adds both region‐based and phase‐based energy functions, is applied to further improve segmentation results. The DFCN model is trained and tested in dataset 1 which contains 570 BUS images from 89 patients. In dataset 2, a 10‐fold support vector machine (SVM) classifier is employed to verify the diagnostic ability using 460 features extracted from the segmentation results of the proposed method. Results: Advantages of the present method were compared with three state‐of‐the‐art networks; the FCN‐8s, U‐net, and dilated residual network (DRN). Experimental results from 170 BUS images show that the proposed method had a Dice Similarity coefficient of 88.97 ± 10.01%, a Hausdorff distance (HD) of 35.54 ± 29.70 pixels, and a mean absolute deviation (MAD) of 7.67 ± 6.67 pixels, which showed the best segmentation performance. In dataset 2, the area under curve (AUC) of the 10‐fold SVM classifier was 0.795 which is similar to the classification using the manual segmentation results. Conclusions: The proposed automatic method may be sufficiently accurate, robust, and efficient for medical ultrasound applications. [ABSTRACT FROM AUTHOR]

Mineral trioxide aggregate (MTA), as a bioactive material, has a widespread application in clinical practice. To date, the effects of MTA on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs) remain unclear. hPDLSCs were isolated from human periodontal ligament tissues and cultured with MTA conditioned media. Cell counting kit-8 (CCK-8) assay was performed to assess the proliferation capacity of MTA-treated hPDLSCs. Immunofluorescence assay, alkaline phosphatase (ALP) activity, alizarin red staining, real-time RT-PCR, and western blot analyses were used to investigate the odonto/osteogenic capacity of hPDLSCs as well as the involvement of NF-κB and MAPK pathways. ALP activity assay revealed that 2 mg/ml was the optimal concentration for the induction of hPDLSCs by MTA. The protein expression of DSP, RUNX2, OCN, OSX, OPN, DMP1, ALP, and COL-I in MTA-treated hPDLSCs was significantly higher than those in control group ( p < 0.01). When hPDLSCs were treated with the inhibitors of NF-κB and MAPK pathways (U0126, SP600125, SB203580, and BMS345541), the effects of MTA on the differentiation of hPDLSCs were suppressed. Mechanistically, P65 was detected to transfer from cytoplasm to nuclei, as indicated by western blot and immunofluorescence assay. Moreover, MAPK-related proteins and its downstream transcription factors were also upregulated in MTA-treated hPDLSCs. Together, mineral trioxide aggregate can promote the odonto/osteogenic capacity of hPDLSCs via activating the NF-κB and MAPK pathways. [ABSTRACT FROM AUTHOR]

Objectives: This work focused on extracting novel and validated digital high‐throughput features to present a detailed and comprehensive description of the American College of Radiology Breast Imaging Reporting and Data System (BI‐RADS) with the goal of improving the accuracy of ultrasound breast cancer diagnosis. Methods: First, the phase congruency approach was used to segment the tumors automatically. Second, high‐throughput features were designed and extracted on the basis of each BI‐RADS category. Then features were selected based on the basis of a Student t test and genetic algorithm. Finally, the AdaBoost classifier was used to differentiate benign tumors from malignant ones. Results: Experiments were conducted on a database of 138 pathologically proven breast tumors. The system was compared with 6 state‐of‐art BI‐RADS feature extraction methods. By using leave‐one‐out cross‐validation, our system achieved a highest overall accuracy of 93.48%, a sensitivity of 94.20%, a specificity of 92.75%, and an area under the receiver operating characteristic curve of 95.67%, respectively, which were superior to those of other methods. Conclusions: The experiments demonstrated that our computerized BI‐RADS feature system was capable of helping radiologists detect breast cancers more accurately and provided more guidance for final decisions. [ABSTRACT FROM AUTHOR]

Purpose Digital Breast Imaging Reporting and Data System ( BI- RADS) features extracted from ultrasound images are essential in computer-aided diagnosis, prediction, and prognosis of breast cancer. This study focuses on the reproducibility of quantitative high-throughput BI- RADS features in the presence of variations due to different segmentation results, various ultrasound machine models, and multiple ultrasound machine settings. Methods Dataset 1 consists of 399 patients with invasive breast cancer and is used as the training set to measure the reproducibility of features, while dataset 2 consists of 138 other patients and is a validation set used to evaluate the diagnosis performances of the final reproducible features. Four hundred and sixty high-throughput BI- RADS features are designed and quantized according to BI- RADS lexicon. Concordance Correlation Coefficient ( CCC) and Deviation (Dev) are used to assess the effect of the segmentation methods and Between-class Distance ( BD) is used to study the influences of the machine models. In addition, the features jointly shared by two methodologies are further investigated on their effects with multiple machine settings. Subsequently, the absolute value of Pearson Correlation Coefficient (Rabs) is applied for redundancy elimination. Finally, the features that are reproducible and not redundant are preserved as the stable feature set. A 10-fold Support Vector Machine ( SVM) classifier is employed to verify the diagnostic ability. Results One hundred and fifty-three features were found to have high reproducibility ( CCC > 0.9 & Dev < 0.1) within the manual and automatic segmentation. Three hundred and thirty-nine features were stable ( BD < 0.2) at different machine models. Two feature sets shared the same 102 features, in which nine features were highly sensitive to the machine settings. Forty-six features were finally preserved after redundancy elimination. For the validation in dataset 2, the area under curve ( AUC) of the 10-fold SVM classifier was 0.915. Conclusions Three factors, segmentation results, machine models, and machine settings may affect the reproducibility of high-throughput BI- RADS features to various degrees. Our 46 reproducible features were robust to these factors and were capable of distinguishing benign and malignant breast tumors. [ABSTRACT FROM AUTHOR]

The Generalized Equilibrium Feedback Analysis method was used to isolate the contributions of major sea-surface temperature anomaly (SSTA) modes over three oceanic basins to the climate variability of tropical cyclone (TC) genesis number (TCGN) in the peak TC season over the western North Pacific (WNP) between 1970 and 2012. The results show that TCGN variation has a statistically significant response to the first SST mode over the tropical North Pacific (TNP1), Indian Ocean (IOBM) and North Atlantic (NA1). The dominant SSTA modes in the three basins contribute 16.6, 12.1 and 13.6% of total TCGN variance, respectively. Among them, TNP1 and NA1 are primarily responsible for TCGN interdecadal variability, with a contribution of 22 and 14.5% to its interdecadal variance at 96 and 93% confidence levels, respectively. TCGN interannual variability, on the other hand, is significantly influenced by IOBM and NA1 with a contribution of 17.6 and 14.3% of the total interannual variance, respectively. The maximum TCGN variability centres are located in the central WNP and South China Sea. The former is primarily associated with responses of low-level relative vorticity to TNP1 and NA1 and the latter is closely linked to the forcing from IOBM and NA1. [ABSTRACT FROM AUTHOR]

SUMMARY In the context of simulations of wave propagations in unbounded domain, absorbing boundary conditions are often used to truncate the simulation domain to a finite space. Perfectly matched layer (PML) has proven to be an excellent absorbing boundary conditions. However, as this technique was primarily designed for the first-order equation system, it cannot be applied to the second-order equation system directly. In this paper, based on a complex-coordinate stretching technique, we developed a novel, efficient auxiliary-differential equation form of the complex-frequency shifted-PML for the second-order equation system. This facilitates the use of complex-frequency shifted-PML in acoustic simulations based upon wave equations of second-order form. Compared with previous state-of-the-art methods, the proposed one has the advantage of simpler implementation. It is an unsplit-field scheme that can be extended to higher-order discretization schemes conveniently. Numerical results from both homogeneous and heterogeneous computational domains are provided to illustrate the validity of the method. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: Assessment of the fetal cerebellar volume on 3D ultrasound data sets is very important in the clinical evaluation of the fetal growth and health. However, the irregular shape of the cerebellum and the strong artifacts of ultrasound images complicate the segmentation without manual intervention. In this paper, the authors propose an approach to locate the cerebellum automatically, which is considered as a prework of the segmentation. Methods: The authors present a weighted Hough transform and a constrained randomized Hough transform to detect the fetal brain midline and the skull, respectively. By combining the location information of these two structures with local image features, a constrained probabilistic boosting tree is then proposed to search the cerebellum. Results: This algorithm was tested on ultrasound volumes of the fetal head with the gestational age ranging from 20 to 33 weeks. Compared with manual measurements, this algorithm obtained a satisfactory performance with the mean Dice similarity coefficient of 0.92 and the average processing time of 0.75 s per case. Conclusions: The results demonstrate that the proposed method is an automatic, fast, and accurate tool for searching the fetal cerebellum on ultrasound volumes. [ABSTRACT FROM AUTHOR]

Purpose: Estimating the fluid motion in ultrasonic videos is a crucial step in the analysis of duodenogastric reflux. Severe image noise and illumination changes in the pyloric region (the region of interest) challenge the accurate estimation of gastric flow. In this paper, the authors propose an illumination-robust optical flow method based on the weighted cross-correlation. Methods: Cross-correlation was combined with the variational optical method framework as an illumination-robust local feature identifier. In consideration of accuracy near edges, they constructed visual similarity weights according to the characteristics of ultrasonic images. A processing procedure containing coarse-to-fine step and refinement was designed to get the final results. They tested the proposed method on synthetic and real ultrasonic images and compared it with other three optical flow methods. For quantitative evaluation, two metrics of angular and amplitude error were used. Results: The synthetic results demonstrate that the proposed method performs better on ultrasonic images, with angular error of 4.1° and amplitude error of 3.3%. In qualitative comparison, the proposed method kept the motion field smooth in the homogeneous region while preserving edge information. When they used the results of the proposed method to judge the gastric flow direction, the automatic judgments agreed well with visual observation. Conclusions: The proposed method is a good tool for image velocimetry in ultrasonic images. It provides promising results to estimate the motion of gastric flow in ultrasonic videos. [ABSTRACT FROM AUTHOR]

Abstract: Two crucial growth factors, FGF2 and TGFβ1, were investigated in this study to determine their inductive effects on the odontoblastic differentiation of human dental pulp stem cells (DPSCs) in vitro. DPSCs were isolated by immunomagnetic bead selection using the STRO-1 antibody, and then co-cultured respectively with FGF2, TGFβ1 and FGF2+TGFβ1. The results showed that FGF2 can exert a significant effect on the cell proliferation, while TGFβ1 or FGF2+TGFβ1 can initiate an odontoblast-like differentiation of DPSCs. Moreover, FGF2 can synergistically upregulate the effects of TGFβ1 on the odontoblastic differentiation of DPSCs, as indicated by the increased alkaline phosphatase activity, the polarized cell appearance and secretary ultrastructural features, the formation of mineralized nodules and the gene/protein expression of dentin sialoprotein and dentin matrix protein-1. Together, FGF2 acted primarily on the cell proliferation, while TGFβ1 and FGF2+TGFβ1 mainly stimulated the odontoblastic differentiation of DPSCs. This study provides interesting progress in the odontoblastic differentiation of DPSCs induced by FGF2 and TGFβ1. [Copyright &y& Elsevier]

Objectives: Oestrogen receptor (ER) is a common nucleus receptor that is essential for the regulation of cell growth, proliferation and differentiation. This study was to examine whether ERα can affect the proliferation and odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs). Materials and Methods: Stem cells from apical papillas were isolated, purified and then transfected with ERα lentiviruses. The proliferation capacity was investigated by cell counting kit‐8 (CCK‐8) assay and flow cytometry. The odonto/osteogenic differentiation ability was analysed by alkaline phosphatase (ALP) activity, alizarin red staining, western blot assay (WB) and real‐time RT‐PCR. MAPK pathway and its downstream transcriptional factors were explored by WB assay. Results: As indicated by CCK‐8 assay and flow cytometry, ERα had no significant effect on the proliferation of SCAPs. When ERα was overexpressed, the ALP activity and the formation of calcified nodules were significantly enhanced in SCAPs. Moreover, the odonto/osteogenic markers (DMP1/DMP1, DSPP/DSP,RUNX2/RUNX2, OCN/OCN) in SCAPs were significantly up‐regulated at both mRNA and protein levels. On the contrary, the odonto/osteogenic differentiation ability of SCAPs was remarkably inhibited after suppression of ERα. Mechanistically, the protein levels of phosphorylated ERK and JNK significantly increased after ERα overexpression. Moreover, some downstream transcriptional factors of MAPK pathway were simultaneously activated by ERα overexpression. Conclusions: Together, the data accumulated here indicated that ERα can enhance the odonto/osteogenic differentiation of SCAPs via ERK and JNK MAPK pathways. [ABSTRACT FROM AUTHOR]

A correction to the article "Contribution of major SSTA modes to the climate variability of tropical cyclone genesis frequency over the western North Pacific" that was published in the February 3, 2016 issue is presented

Background Information: Immature dental papilla stem cells and mature dental pulp stem cells are capable of performing the dentinogenesis under suitable circumstances. However, a dentinogenic comparison between immature and mature dental root stem cells remains unknown., Results: iRPSCs (immature root papilla stem cells) at the root-forming stage and mRPSCs (mature root pulp stem cells) at the root-completed stage were isolated from 16-day-old and 8-week-old rat first molar roots, respectively. Growth kinetics and flow cytometry results showed that iRPSCs presented more active proliferation properties than mRPSCs. Their odontoblastic differentiation and dentinogenic potential were subsequently compared both in vitro and in vivo. iRPSCs exhibited a more potent odontoblastic differentiation than mRPSCs in vitro, as indicated by the higher levels of gene expression for dentin sialophosphoprotein and ALP (alkaline phosphatase), increased protein expression of dentin sialoprotein and runt-related transcription factor 2, decreased gene/protein expression for osterix/osteocalcin (osteogenic markers), elevated ALP activity and enhanced calcium deposition in the mineralization-inducing media. Allotransplantation results demonstrated that all iRPSCs pellets in vivo performed typical dentinogenesis, whereas mRPSCs pellets mainly produced bone-like tissues., Conclusion: iRPSCs presented stronger dentinogenesis but weaker osteogenesis than did mRPSCs, suggesting that the dentinogenic competence of root mesenchymal stem cells decreases, whereas their osteogenic potential the increases following the maturation of the tooth root.

Background Information: Although the mechanism of cementogenesis is an area full of debate, the DFCs (dental follicle cells) are thought to be the precursors of cementoblasts. At the onset of cementogenesis, DFCs come into contact with the root dentin surface and undergo subsequent differentiation. But the exact effects of dentin or dentin matrix on DFCs remain an open question. In the present study, we hypothesized that dNCPs (dentin non-collagenous proteins) extracted from dentin could stimulate DFCs to differentiate into cementoblast lineages., Results: DFCs were isolated from tooth germs of SD (Sprague-Dawley) rats and then co-cultured with dNCPs. Treated DFCs presented several features of cementoblast lineages in vitro, as indicated by morphological changes, decreased proliferation, enhanced ALP (alkaline phosphatase) activity and increased matrix mineralization. The expression of mineralization-associated proteins and genes were up-regulated after induction, whereas the expression of specific markers of odontoblast were not detected. Incubation of treated DFC pellets in vivo revealed that a large amount of cementum-like tissues was formed within the novel dentin carriers, which were quite distinct from the newly formed osteodentin secreted by DPSCs (dental pulp stem cells). The negative expression of DSP (dentin sialoprotein) also excluded the possibility of producing dentin matrix by treated DFCs., Conclusions: dNCPs can stimulate DFCs to differentiate into cementoblast lineages. The present study provides new insights into the mechanism of cementogenesis.

Background Information: Although adult bone-marrow-derived cell populations have been used to make teeth when recombined with embryonic oral epithelium, the differences between dental and non-dental stem-cell-mediated odontogenesis remain an open question., Results: STRO-1(+) (stromal precursor cell marker) DPSCs (dental pulp stem cells) and BMSSCs (bone marrow stromal stem cells) were isolated from rat dental pulp and bone marrow respectively by magnetic-activated cell-sorting techniques. Their odontogenic capacity was compared under the same inductive microenvironment produced by ABCs (apical bud cells) from 2-day-old rat incisors. Co-cultured DPSCs/ABCs in vitro showed more active odontogenic differentiation ability than mixed BMSSCs/ABCs, as indicated by the accelerated matrix mineralization, up-regulated alkaline phosphatase activity, cell-cycle modification, and the expression of tooth-specific proteins and genes. After cultured for 14 days in the renal capsules of rat hosts, recombined DPSC/ABC pellets formed typical tooth-shaped tissues with balanced amelogenesis and dentinogenesis, whereas BMSSC/ABC recombinants developed into atypical dentin-pulp complexes without enamel formation. DPSC and BMSSC pellets in vivo produced osteodentin-like structures and fibrous connective tissues respectively., Conclusions: DPSCs presented more striking odontogenic capability than BMSSCs under the induction of postnatal ABCs. This report provides critical insights into the selection of candidate cells for tooth regeneration between dental and non-dental stem cell populations.