Nonergodicity of confined superdiffusive fractional Brownian motion.

Using stochastic simulations supported by analytics we determine the degree of nonergodicity of box-confined fractional Brownian motion for both sub- and superdiffusive Hurst exponents H. At H>1/2 the nonequivalence of the ensemble- and time-averaged mean-squared displacements (TAMSDs) is found to be most pronounced (with a giant spread of individual TAMSDs at H→1), with two distinct short-lag-time TAMSD exponents.

Anomalous diffusion, nonergodicity, non-Gaussianity, and aging of fractional Brownian motion with nonlinear clocks.

How do nonlinear clocks in time and/or space affect the fundamental properties of a stochastic process? Specifically, how precisely may ergodic processes such as fractional Brownian motion (FBM) acquire predictable nonergodic and aging features being subjected to such conditions? We address these questions in the current study. To describe different types of non-Brownian motion of particles-including power-law anomalous, ultraslow or logarithmic, as well as superfast or exponential diffusion-we here develop and analyze a generalized stochastic process of scaled-fractional Brownian motion (SFBM). The time- and space-SFBM processes are, respectively, constructed based on FBM running with nonlinear time and space clocks. The fundamental statistical characteristics such as non-Gaussianity of particle displacements, nonergodicity, as well as aging are quantified for time- and space-SFBM by selecting different clocks. The latter parametrize power-law anomalous, ultraslow, and superfast diffusion. The results of our computer simulations are fully consistent with the analytical predictions for several functional forms of clocks. We thoroughly examine the behaviors of the probability-density function, the mean-squared displacement, the time-averaged mean-squared displacement, as well as the aging factor. Our results are applicable for rationalizing the impact of nonlinear time and space properties superimposed onto the FBM-type dynamics. SFBM offers a general framework for a universal and more precise model-based description of anomalous, nonergodic, non-Gaussian, and aging diffusion in single-molecule-tracking observations.

Fractal relaxation model with a nonlinear diffusion coefficient for fitting anomalous diffusion data in magnetic resonance imaging.

In this paper a relaxation model of signal attenuation in diffusion-weighted magnetic resonance imaging (dMRI) with varying diffusion coefficient in terms of fractal derivative is proposed, in which the diffusion coefficient is a power law of the effective diffusion time. The relaxation model provides measures of diffusion constant, fractal dimension of diffusive trajectory of water molecule and the time power-law behavior of the diffusion coefficient. The proposed model was used to describe the magnetic resonance attenuation signal of the bullfrog sciatic nerve, and the corresponding spectral entropy was calculated to detect the environmental complexity in bullfrog sciatic nerve for water molecular diffusion. The results showed that the fractal derivative relaxation model (the VDC model) can accurately depict the diffusion pattern of water molecules in complex heterogeneous biological media at large b values. The VDC model provides an alternative theoretical reference for biological tissue detection based on time-dependent diffusion of water molecules.

Anomalous diffusion, non-Gaussianity, and nonergodicity for subordinated fractional Brownian motion with a drift.

The stochastic motion of a particle with long-range correlated increments (the moving phase) which is intermittently interrupted by immobilizations (the trapping phase) in a disordered medium is considered in the presence of an external drift. In particular, we consider trapping events whose times follow a scale-free distribution with diverging mean trapping time. We construct this process in terms of fractional Brownian motion with constant forcing in which the trapping effect is introduced by the subordination technique, connecting "operational time" with observable "real time." We derive the statistical properties of this process such as non-Gaussianity and nonergodicity, for both ensemble and single-trajectory (time) averages. We demonstrate nice agreement with extensive simulations for the probability density function, skewness, kurtosis, as well as ensemble and time-averaged mean-squared displacements. We place a specific emphasis on the comparisons between the cases with and without drift.

A concise continuous time random-walk diffusion model for characterization of non-exponential signal decay in magnetic resonance imaging.

Diffusion-weighted magnetic resonance imaging (dMRI) is a method of capturing the signal of water molecules diffusing in heterogeneous materials. Gaussian diffusion is interrupted when water mobility is hampered by obstructions in complex structures, and the dMRI signal decay does not match the single exponential decay in Brownian motion. In this study, a concise continuous time random-walk diffusion model is derived with less parameters than the continuous time random walk (CTRW) model and used to characterize the attenuation signal of brain tissue. The fitting results are compared with the CTRW model and the mono-exponential model reflecting the sub-diffusion and the long tail phenomenon of signal decay. Three sample experiments on rat brain and human brain are chosen to evaluate the validity in explaining the anomalous diffusion of water molecules in biological tissues, particularly in brain tissues in diverse directions, which also extends the applications of the concise continuous time random-walk diffusion model. Furthermore, we note that the concise continuous time random-walk diffusion model has practical advantages over the classical exponential model from the perspective of computational accuracy especially in the case of large b values, and has less parameters and is comparable to the CTRW model.

Effectiveness of Group Patient-Led Life Skills Training on Function and Self-Efficacy for People With Schizophrenia: A Quasi-Experimental Study.

The current quasi-experimental study evaluated the effectiveness of group patient-led life skills training (LST) on functional recovery and self-efficacy of people with schizophrenia. Two psychiatric units in a mental health center were randomly assigned to intervention (first psychiatric unit) and control (second psychiatric unit) groups. Convenience sampling was used to recruit participants. The intervention group (n = 51) received group patient-led LST, and the control group (n = 53) received routine mental health care services. Outcomes on patients' functional recovery and self-efficacy between groups were compared at baseline, during the intervention (4 weeks), and immediately after the intervention (8 weeks). Repeated measures analysis of variance was used to analyze the data. Results showed that the intervention improved functional recovery and self-efficacy of people with schizophrenia (p < 0.05). Therefore, it is recommended that group patient-led LST be integrated in therapy for people with schizophrenia to facilitate their functional recovery and help them achieve their highest potential for independent living. [Journal of Psychosocial Nursing and Mental Health Services, 61(2), 60-67.].

Sleep Misperception and Associated Factors in Patients With Anxiety-Related Disorders and Complaint of Insomnia: A Retrospective Study.

Purpose: Data on sleep parameters by polysomnography (PSG) in patients with anxiety-related disorders are limited. Although the disturbance and risk factors of sleep misperception have been implicated in psychopathology, its role in anxiety-related disorders remains unclear. This retrospective study aimed to explore the characteristics and sleep parameters in patients with anxiety-related disorders and different sleep perception types, and to explore the associated factors for sleep misperception. Methods: Patients with anxiety-related disorders who had complaint of insomnia for more than 3 months were collected at Wuhan Mental Health Center between December 2019 and July 2021. Patients underwent a two-night PSG monitoring and completed a self-reported sleep questionnaire. Behaviors were assessed using 30-item Nurses' Observation Scale for Inpatient Evaluation (NOSIE-30). Patients were divided into normal sleep perception (NSP), positive sleep perception abnormality [PSPA; overestimation of total sleep time (TST) >60 min], and negative sleep perception abnormality (NSPA; underestimation of TST >60 min) groups. PSG indicators and NOSIE-30 scores were compared among groups using the one-way analysis of variance and the Kruskal-Wallis test. Multiple linear regression analysis was performed to determine the associated factors for misperception index. Results: The subjective and objective TST were 5.5 ± 1.9 h and 6.4 ± 1.7 h in 305 patients, respectively. Sixty-nine (22.6%) had PSPA, 80 (26.2%) had NSP, and 156 (51.1%) had NSPA. Subjective TST and objective sleep parameters were significantly different among groups. No statistical differences in NOSIE-30 subscale and total scores were observed among groups. Sex, rapid eye movement (REM)/TST (%), sleep efficiency, number of awakenings, Non-rapid eye movement of stage 2 sleep (NREM)/TST (%), REM spontaneous arousal times, sleep latency, diagnosis, social competence, and manifest psychosis were associated with sleep misperception. Conclusion: Sleep misperception is common in patients with anxiety-related disorders. Various sleep perception types have different PSG profiles, but similar personal and social behaviors. These data may be helpful to conduct personalized treatment.

Suicidal Ideation and Mental Health Help-Seeking Behaviors Among Older Chinese Adults During the COVID-19 Pandemic.

OBJECTIVE: To examine prevalence and correlates of suicidal ideation in older Chinese adults (OCAs) during the COVID-19 pandemic, as well as mental health help-seeking behaviors of suicidal OCAs. BACKGROUND: Few data on suicidal behaviors of older adults during the pandemic are available. METHODS: In this cross-sectional survey, 1159 OCAs completed an online self-administered questionnaire between 23 February and 25 March 2020. A standardized single question and the 12-item General Health Questionnaire were used to assess the presence of suicidal ideation and common mental health problems (CMHPs), respectively. Suicidal ideators were further asked about their perceived need for mental health care and help-seeking from mental health workers. RESULTS: 4.1% of the OCAs experienced suicidal ideation during the past 2 weeks. Among the suicidal OCAs, 31.9% perceived a need for mental health care but only 10.6% had sought help from mental health workers. Factors significantly associated with suicidal ideation were a marital status of "others" (OR=2.39, P = .021), disagreement regarding the successful containment of the pandemic (OR=2.43, P = .022), physical health problems (OR=2.23, P = .012), and CMHPs (OR=4.99, P < .001). CONCLUSIONS: During the COVID-19 pandemic, OCAs constitute a subpopulation that needs mental health services for suicidal problems but tends not to seek mental health help. Mental health services for OCAs may include mental health education, periodic evaluation of risk of suicide, expanded psychosocial support, and, when necessary, psychological crisis intervention and psychiatric treatment.

A quantitative detection of mung bean in chestnut paste using duplex digital PCR.

Highly manufacturing process of chestnut paste leaves a considerable space for Economically Motivated Adulteration (EMA) with cheaper ingredients such as mung bean. In this paper a novel quantitative detection of mung bean in chestnut paste using duplex digital PCR was reported. Two sets of primers and probes were designed according to mung bean and chestnut specific genomic genes suitable for duplex droplet digital PCR (ddPCR) and duplex chip digital PCR (cdPCR) to set up a mass ratio quantitative detection method for mung bean, a common alternative plant-derived ingredient in chestnut paste products. The manufacturing process of chestnut paste products was considered to establish the linear relationship formula between mass ratio and gene copy number (CN) ratio of the two ingredients. The limits of quantification for gene CN concentrations (LOQcopy) of mung bean and chestnut were both 6 copies/µL, at the same time a mass ratio of mung bean in chestnut paste range from 5% to 80% was able to be quantified accurately to provide technical support for the identification of fraudulent substitution or adventitious contamination.

SELL and IFI44 as potential biomarkers of Sjögren's syndrome and their correlation with immune cell infiltration.

The onset of Sjögren's syndrome (SS) is hidden, early diagnosis is difficult, and the disorder seriously endangers the physical and mental health of affected people. This study aims to identify potential biomarkers of SS and to investigate the characteristics of immune cell infiltration. We used four SS gene expression profile data series from the Gene Expression Omnibus database, and applied bioinformatics analysis and machine learning algorithms to screen two biomarkers, SELL (L-selectin) and IFI44 (interferon-induced protein 44), from 101 differentially expressed genes. The two-gene model comprising SELL and IFI44 showed good diagnostic ability for SS in the training set (AUC = 0.992) and verification set (AUC = 0.917). Analysis of infiltrating immune cells in SS identified naive B cells, resting CD4 memory T cells, activated CD4 memory T cells, gamma delta T cells, M0 macrophages, M1 macrophages, plasma cells, CD8 T cells, activated NK cells and monocytes as candidate participants in the SS process. Furthermore, SELL was associated with M2 macrophages, activated CD4 memory T cells, gamma delta T cells, resting NK cells and plasma cells, while IFI44 was associated with activated mast cells, resting NK cells, resting mast cells and CD8 T cells. This study demonstrates that SELL and IFI44 can serve as good diagnostic markers for SS and may also be new diagnostic and therapeutic targets for SS.

Relative Entropy Method Applied for the Fatigue Life Distribution of Carbon Fiber/Epoxy Composites.

This paper verifies the feasibility of the relative entropy method in selecting the most suitable statistical distribution for the experimental data, which do not follow an exponential distribution. The efficiency of the relative entropy method is tested through the fractional order moment and the logarithmic moment in terms of the experimental data of carbon fiber/epoxy composites with different stress amplitudes. For better usage of the relative entropy method, the efficient range of its application is also studied. The application results show that the relative entropy method is not very fit for choosing the proper distribution for non-exponential random data when the heavy tail trait of the experimental data is emphasized. It is not consistent with the Kolmogorov-Smirnov test but is consistent with the residual sum of squares in the least squares method whenever it is calculated by the fractional moment or the logarithmic moment. Under different stress amplitudes, the relative entropy method has different performances.

Reaction and ultraslow diffusion on comb structures.

A two-dimensional (2D) comb model is proposed to characterize reaction-ultraslow diffusion of tracers both in backbones (x direction) and side branches (y direction) of the comblike structure with two memory kernels. The memory kernels include Dirac delta, power-law, and logarithmic and inverse Mittag-Leffler (ML) functions, which can also be considered as the structural functions in the time structural derivative. Based on the comb model, ultraslow diffusion on a fractal comb structure is also investigated by considering spatial fractal geometry of the backbone volume. The mean squared displacement (MSD) and the corresponding concentration of the tracers, i.e., the solution of the comb model, are derived for reactive and conservative tracers. For a fractal structure of backbones, the derived MSDs and corresponding solutions depend on the backbone's fractal dimension. The proposed 2D comb model with different kernel functions is feasible to describe ultraslow diffusion in both the backbone and side branches of the comblike structure.

Application of nomograms to predict overall and cancer-specific survival in patients with chordoma.

BACKGROUND: The survival prediction of patients with chordoma is difficult to make due to the rarity of this oncologic disease. Our objective was to apply a nomogram to predict survival outcomes in individuals with chordoma of the skull base, vertebral column, and pelvis. METHODS: A total of 558 patients with chordoma between 1973 and 2014 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors in patients with chordoma were identified via univariate and multivariate Cox analysis. Then these prognostic factors were incorporated into a nomogram to predict 3- and 5-year overall survival and cancer-specific survival rates. Internal and external data were used to validate the nomograms. Concordance indices (C-indices) were used to estimate the accuracy of this nomogram system. RESULTS: A total of 558 patients were randomly assigned into a training cohort (n = 372) and a validation cohort (n = 186). Age, surgical stage, tumor size, histology, primary site, and use of surgery were identified as independent prognostic factors via univariate and multivariate Cox analysis (all p < 0.05) and further included to establish the nomogram. The C-indices for overall survival and cancer-specific survival prediction of the training cohort were 0.775 (95% confidence interval, 0.770-0.779) and 0.756 (95% confidence interval, 0.749 -0.762). The calibration plots both showed an excellent consistency between actual survival and nomogram prediction. CONCLUSION: Nomograms were constructed to predict overall survival and cancer-specific survival for patients with chordoma of the skull base, vertebral column, and pelvis. The nomogram could help surgeons to identify high risk of mortality and evaluate prognosis in patients with chordoma.

Diffusion Tensor Magnetic Resonance Imaging in Chronic Spinal Cord Compression.

Chronic spinal cord compression is the most common cause of spinal cord impairment in patients with nontraumatic spinal cord damage. Conventional magnetic resonance imaging (MRI) plays an important role in both confirming the diagnosis and evaluating the degree of compression. However, the anatomical detail provided by conventional MRI is not sufficient to accurately estimate neuronal damage and/or assess the possibility of neuronal recovery in chronic spinal cord compression patients. In contrast, diffusion tensor imaging (DTI) can provide quantitative results according to the detection of water molecule diffusion in tissues. In the present study, we develop a methodological framework to illustrate the application of DTI in chronic spinal cord compression disease. DTI fractional anisotropy (FA), apparent diffusion coefficients (ADCs), and eigenvector values are useful for visualizing microstructural pathological changes in the spinal cord. Decreased FA and increases in ADCs and eigenvector values were observed in chronic spinal cord compression patients compared to healthy controls. DTI could help surgeons understand spinal cord injury severity and provide important information regarding prognosis and neural functional recovery. In conclusion, this protocol provides a sensitive, detailed, and noninvasive tool to evaluate spinal cord compression.

Time course of diffusion tensor imaging metrics in the chronic spinal cord compression rat model.

BACKGROUND: Diffusion tensor imaging (DTI) provides information about water molecule diffusion in spinal cord. PURPOSE: This study was aimed to investigate DTI changes in the different stages of compressive spinal cord induced by water-absorbing material implantation. MATERIAL AND METHODS: The spinal cord compression was administered over the fourth cervical vertebral level in rat. Rat models were divided into five subgroups according to compression stages: sham group, group A: three-day compression rat models; group B: 12-day compression rat models; group C: 20-day compression rat models; group D: 60-day compression rat models. DTI including fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in the compressive spinal cord were collected. The relationship between the Basso, Beattie, and Bresnahan (BBB) scores and DTI metrics was further explored. RESULTS: Compared with the sham group, BBB scoring of rat model showed a decreased tendency from group A ( P < 0.05) to group B ( P < 0.05). Then the motor function of rat model hindlimbs was recovered in some degree from group C ( P < 0.05) to group D ( P < 0.05) but had significant motor defects when compared with the normal level ( P < 0.05). The DTI metrics results revealed that chronic spinal cord compression resulted in lower FA value and higher ADC value at the compressive spinal cord level assessed at all four time-points ( P < 0.05). DTI metrics also showed a close correlation with motor function ( P < 0.05). CONCLUSION: DTI is an optimal pre-clinical imaging tool to reflect locomotor performance and pathological status of compressive spinal cord epicenter in chronic spinal cord compression rat model.

Nomogram application to predict overall and cancer-specific survival in osteosarcoma.

PURPOSE: A prognostic nomogram was applied to predict survival in osteosarcoma patients. PATIENTS AND METHODS: Data collected from 2,195 osteosarcoma patients in the Surveillance, Epidemiology, and End Results (SEER) database between 1983 and 2014 were analyzed. Independent prognostic factors were identified via univariate and multivariate Cox analyses. These were incorporated into a nomogram to predict 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates. Internal and external data were used for validation. Concordance indices (C-indices) were used to estimate nomogram accuracy. RESULTS: Patients were randomly assigned into a training cohort (n=1,098) or validation cohort (n=1,097). Age at diagnosis, tumor site, histology, tumor size, tumor stage, use of surgery, and tumor grade were identified as independent prognostic factors via univariate and multivariate Cox analyses (all P<0.05) and then included in the prognostic nomogram. C-indices for OS and CSS prediction in the training cohort were 0.763 (95% CI 0.761-0.764) and 0.764 (95% CI 0.762-0.765), respectively. C-indices for OS and CSS prediction in the external validation cohort were 0.739 (95% CI 0.737-0.740) and 0.740 (95% CI, 0.738-0.741), respectively. Calibration plots revealed excellent consistency between actual survival and nomogram prediction. CONCLUSION: Nomograms were constructed to predict OS and CSS for osteosarcoma patients in the SEER database. They provide accurate and individualized survival prediction.

Hydroxy metabolites of polychlorinated biphenyls (OH-PCBs) exhibit inhibitory effects on UDP-glucuronosyltransferases (UGTs).

Hydroxy metabolites of polychlorinated biphenyls (OH-PCBs) are important substance basis for the toxicity of PCBs. This study aims to investigate the inhibition of OH-PCBs on the activity of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of PCBs from a new perspective. In vitrohuman recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used as the probe reaction. The number of chlorine atom can affect the inhibition potential of OH-PCBs towards different isoforms of UGTs, and complex structure-activity relationship was found for the inhibition of OH-PCBs on the activities of UGT isoforms. For the inhibition kinetic determination, 2'OHPCB106 and 4'OHPCB106 were selected as the representative OH-PCBs, and UGT1A1, 1A7, and 2B7 were chosen as the representative UGT isoforms. Competitive inhibition of 2'OHPCB106 and 4'OHPCB106 on the activities of UGT1A1, UGT1A7, and UGT2B7 was found. For 2'OHPCB106, the inhibition kinetic parameters (Ki) were calculated to be 0.4 µM for UGT1A1, 1.3 µM for UGT1A7, and 2.7 µM for UGT2B7, respectively. For 4'OHPCB106, Ki values were calculated to be 0.7 µM for UGT1A1, 6.8 µM for UGT1A7, and 4.8 µM for UGT2B7, respectively. In silico docking method was utilized to elucidate the inhibition difference of UGT1A1 by four OH-PCBs with similar structures (4'OHPCB9, 4'OHPCB26, 4'OHPCB112 and 4'OHPCB165). In conclusion, these data will be helpful for understanding the toxicity mechanisms of PCBs from a view of metabolic interference.

Identification of key target genes and biological pathways in multiple sclerosis brains using microarray data obtained from the Gene Expression Omnibus database.

OBJECTIVE: The purpose of this study was to investigate critical genes in multiple sclerosis (MS) using microarray data from brain tissue in MS. MATERIALS: The expression profile data set of MS (GSE38010) downloaded from the Gene Expression Omnibus database contained gene information from five plaque tissues from MS brains and two white matter tissues from healthy controls. An R package was applied to process these raw chip data. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network analysis were performed to investigate interactions between differentially expressed genes (DEGs) in MS brain tissues. RESULTS: This study identified a total of 1065 DEGs, including 530 up-regulated genes and 535 down-regulated genes, in MS brain tissue samples compared to those in normal white matter tissue samples. GO and KEGG pathway enrichment analyses showed that the up-regulated DEGs were mainly related to neuron development, neuron projection morphogenesis and neuron differentiation. Furthermore, the down-regulated DEGs were largely related to axon ensheathment, ensheathment of neurons and nervous system development. Seven key genes were found as hub genes in the maintenance of the PPI network. CONCLUSION: Several key target genes and their GO and KEGG pathway enrichment identified in the present study may serve as feasible targets for MS therapies.

Application of Diffusion Tensor Imaging Cutoff Value to Evaluate the Severity and Postoperative Neurologic Recovery of Cervical Spondylotic Myelopathy.

BACKGROUND: Magnetic resonance imaging (MRI) plays an important role in the assessment of spinal cord status for cervical spondylotic myelopathy (CSM). Diffusion tensor imaging (DTI) also is a novel investigation tool with good sensitivity to detect changes in CSM, but it is not routinely used in spinal cord evaluation. METHODS: Sixty-six patients with CSM who required surgical decompression were included. All the patients were divided into 4 subgroups according to Japanese Orthopaedic Association (JOA) recovery rate. A 3.0T MR system was applied to obtain DTI of the spinal cord. Clinical assessment was performed with the JOA scores system. RESULTS: DTI data of 61 patients were available for further analysis in this study. No significant differences in age, sex, cervical curvature, surgical approach, and preoperative JOA score between the 4 subgroups were found (P > 0.05). Significant differences in apparent diffusion coefficient (ADC) (P < 0.0001), mean diffusivity (MD), (P < 0.0001), axial diffusivity (AD) (P = 0.0459), and radial diffusivity (RD) (P < 0.0001) values were found between the 4 groups. The ADC (P < 0.0001), MD (P < 0.0001), AD (P = 0.0434), and RD (P < 0.0001) values were significantly correlated with JOA recovery rate. Cutoff values of ADC, MD, AD, and RD in this study were 1.378*10-3, 1.378*10-3, 2.386*10-3, and 0.894*10-3 mm2/s, respectively. CONCLUSION: DTI was closely related to the severity of CSM, and cutoff values of DTI enabled the surgeons to predict the surgical outcomes in patients with CSM. These evaluation metrics may reflect the pathologic conditions of the spinal cord quantitatively, and potentially evaluate the functional status of spinal cords.

Down-regulation of tumor endothelial marker 8 suppresses cell proliferation mediated by ERK1/2 activity.

Tumor endothelial marker 8 (TEM8) was recently suggested as a putative anti-tumor target in several types of human cancer based on its selective overexpression in tumor versus normal endothelial cells. The objective of this study was to detect the potential functions of TEM8 in osteosarcoma. Overall, TEM8 was mainly located in cytoplasm and was up-regulated in osteosarcoma compared to benign bone lesions and adjacent non tumor tissue (ANT). High TEM8 expression group had a significant lower overall survival rate than that in the low TEM8 expression group. TEM8 knock-down by siRNA or shRNA results in significant reduction of osteosarcoma cell growth and proliferation both in vitro and in vivo. Ablation of TEM8 led to increasing of p21 and p27 and suppression of cyclin D1 mediated by Erk1/2 activity. These findings suggest that down-regulation of TEM8 play an important role in the inhibition of tumorigenesis and development of osteosarcoma.