Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Osteosarcoma (OS) is the most common malignant primary bone tumor in children and adolescents and features rapid development, strong metastatic ability, and poor prognosis. It has been well established that diverse genetic aberrations and metabolic alterations confer the tumorigenesis and development of OS. The intricate metabolism and vascularization that contributes to the nutrient and structural support for tumor progression should be thoroughly clarified to help us gain novel insights into OS and its clinical diagnoses and treatments. With regard to the complex bone extracellular matrix (ECM) and local cell populations, we intend to illustrate the interrelationship between various microenvironmental signals and the different stages of OS evolution. Solid evidence has noted two crucial factors of the OS microenvironment in the acquisition of stem cell phenotypes - transforming growth factor-β1 (TGF-β1) signaling and hypoxia. Different cell subtypes in the local environment might also serve as unique contributors that interact with each other and communicate with distant cells, thus participating in local invasion and metastasis. Proper models have been established and improved to reveal the evolutionary footsteps of how normal cells transform into a neoplastic state and progress toward malignancy

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL) in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA), and connective tissue growth factor (CTGF); increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2); increased oxidative stress and reactive oxygen species- (ROS-) inducing enzymes (NOX2 and iNOS); dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity). Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models

Developing a Semantic-Driven Hybrid Segmentation Method for Point Clouds of 3D Shapes

With the rapid development of point cloud processing technologies and the availability of a wide range of 3D capturing devices, a geometric object from the real world can be directly represented digitally as a dense and fine point cloud. Decomposing a 3D shape represented in point cloud into meaningful parts has very important practical implications in the fields of computer graphics, virtual reality and mixed reality. In this paper, a semantic-driven automated hybrid segmentation method is proposed for 3D point cloud shapes. Our method consists of three stages: semantic clustering, variational merging, and region remerging. In the first stage, a new feature of point cloud, called Local Concave-Convex Histogram, is introduced to first extract saddle regions complying with the semantic boundary feature. All other types of regions are then aggregated according to this extracted feature. This stage often leads to multiple over-segmentation convex regions, which are then remerged by a variational method established based on the narrow-band theory. Finally, in order to recombine the regions with the approximate shapes, order relation is introduced to improve the weighting forms in calculating the conventional Shape Diameter Function. We have conducted extensive experiments with the Princeton Dataset. The results show that the proposed algorithm outperforms the state-of-the-art algorithms in this area. We have also applied the proposed algorithm to process the point cloud data acquired directly from the real 3D objects. It achieves excellent results too. These results demonstrate that the method proposed in this paper is effective and universal

Diagnosing the Ice Crystal Enhancement Factor in the Tropics

Recent modeling studies have revealed that ice crystal number concentration is one of the dominant factors in the effect of clouds on radiation. Since the ice crystal enhancement factor and ice nuclei concentration determine the concentration, they are both important in quantifying the contribution of increased ice nuclei to global warming. In this study, long-term cloud-resolving model (CRM) simulations are compared with field observations to estimate the ice crystal enhancement factor in tropical and midlatitudinal clouds, respectively. It is found that the factor in tropical clouds is ~10 3-104 times larger than that of mid-latitudinal ones, which makes physical sense because entrainment and detrainment in the Tropics are much stronger than in middle latitudes. The effect of entrainment/detrainment on the enhancement factor, especially in tropical clouds, suggests that cloud microphysical parameterizations should be coupled with subgrid turbulence parameterizations within CRMs to obtain a more accurate depiction of cloud-radiative forcing

Causal effects of education attainment on oral and oropharyngeal cancer: New evidence from a meta-analysis and Mendelian randomization study

ObjectivesHigher educational attainment (EA) has proven to be beneficial for preventing and treating various types of cancers. Currently, there is little evidence on the association between EA and prevention of oral cavity and pharyngeal cancer (OCPC).MethodsSeveral databases were searched until October 1, 2022, and a meta-analysis was performed. A Mendelian randomization (MR) study was conducted with EA (i.e., the exposure) data derived from the Social Science Genetic Association Consortium and 6,034 cases of OCPC (i.e., outcome) selected from the Integrative Epidemiology Unit genome-wide association study. Five methods were used to evaluate the causality between EA and OCPC. The leave-one-out sensitivity test, MR-Egger regression, and multivariable MR (MVMR) analysis were applied to evaluate the MR results.ResultsThe meta-analysis included 36 eligible studies. EA was significantly and negatively associated with OCPC risk (odds ratio [OR]: 0.439, 95% confidence interval [CI]: 0.383–0.503, P < 0.001). MR analysis revealed that the risk of OCPC, oropharyngeal cancer, and oral cavity cancer decreased with an increase in education (OR: 0.349, 95% CI: 0.222–0.548, P < 0.001; OR: 0.343, 95% CI: 0.198–0.597; P < 0.001; OR: 0.342, 95% CI: 0.195–0.601, P < 0.001, respectively). Even after correcting for mediators, high EA still significantly reduced the risk of OCPC (OR: 0.361, 95% CI: 0.281–0.463, P < 0.001).ConclusionBoth the meta-analysis and MR results demonstrated that high levels of EA can reduce the risk of OCPC in the general population

A Contribution by Ice Nuclei to Global Warming

Ice nuclei (IN) significantly affect clouds via supercooled droplets, that in turn modulate atmospheric radiation and thus climate change. Since the IN effect is relatively strong in stratiform clouds but weak in convective ones, the overall effect depends on the ratio of stratiform to convective cloud amount. In this paper, 10 years of TRMM (Tropical Rainfall Measuring Mission) satellite data are analyzed to confirm that stratiform precipitation fraction increases with increasing latitude, which implies that the IN effect is stronger at higher latitudes. To quantitatively evaluate the IN effect versus latitude, large-scale forcing data from ten field campaigns are used to drive a CRM (cloud-resolving model) to generate longterm cloud simulations. As revealed in the simulations, the increase in the net downward radiative flux at the TOA (top of the atmosphere) from doubling the current IN concentrations is larger at higher latitude, which is attributed to the meridional tendency in the stratiform precipitation fraction. Surface warming from doubling the IN concentrations, based on the radiative balance of the globe, is compared with that from anthropogenic COZ . It is found that the former effect is stronger than the latter in middle and high latitudes but not in the Tropics. With regard to the impact of IN on global warming, there are two factors to consider: the radiative effect from increasing the IN concentration and the increase in IN concentration itself. The former relies on cloud ensembles and thus varies mainly with latitude. In contrast, the latter relies on IN sources (e.g., the land surface distribution) and thus varies not only with latitude but also longitude. Global desertification and industrialization provide clues on the geographic variation of the increase in IN concentration since pre-industrial times. Thus, their effect on global warming can be inferred and then be compared with observations. A general match in geographic and seasonal variations between the inferred and observed warming suggests that IN may have contributed positively to global warming over the past decades, especially in middle and high latitudes