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Background Recently, increasing attention has been drawn to the impact of the tumor microenvironment (TME) on the occurrence and progression of malignant tumors. A variety of 3D culture techniques have been used to simulate TME in vitro. The purpose of this study was to reveal the differences in transcriptional and metabolic levels between osteosarcoma (OS) 2D cells, 3D cells, 3D cell-printed tissue, isolated tissue, and transplanted tumor tissue in vivo. Methods We cultured the OS Saos-2 cell line under different culture methods as 2D cells, 3D cells, 3D cell-printed tissue and isolated tissue for 14 days and transplanted tumors in vivo as a control group. Through transcriptomic and metabonomic analyses, we determined the changes in gene expression and metabolites in OS tissues under different culture methods. Results At the transcriptional level, 166 differentially expressed genes were found, including the SMAD family, ID family, BMP family and other related genes, and they were enriched in the TGF-β signaling pathway, complement and coagulation cascades, signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, ferroptosis, cGMP-PKG signaling pathway and other pathways. At the metabolic level, 362 metabolites were significantly changed and enriched in metabolic pathways such as the Fc Epsilon RI signaling pathway, histidine metabolism, primary bile acid biosynthesis, steroid biosynthesis, protein digestion and absorption, ferroptosis, and arachidonic acid metabolism. After integrating the transcriptome and metabolomics data, it was found that 44 metabolic pathways were changed, and the significantly enriched pathways were ferroptosis and pyrimidine metabolism. Conclusion Different culture methods affect the gene expression and metabolite generation of OS Saos-2 cells. Moreover, the cell and tissue culture method in vitro cannot completely simulate TME in vivo, and the ferroptosis and pyrimidine metabolism pathways mediate the functional changes of OS Saos-2 cells in different microenvironments.

Enhance human walking and running is much more difficult compared to build a machine to help someone with disability. Unpowered ankle-foot exoskeletons are the current development trend due to their lightweight, wearable, and energy-free features, but the huge recognition and energy control system still affects their practicability. To refine the recognition and control system, we designed an unpowered soft ankle-foot exoskeleton with a purely mechanical self-adaptiveness clutch, which can realize the collection and release of energy according to different gait stage. Through switching and closing of this clutch, energy is collected when the ankle is doing negative work and released when the ankle is doing positive work. Results shows the unpowered ankle-foot exoskeleton at the stiffness of 12000 N/m could relieve muscles' load, with reduction of force by 52.3 % and 5.2%, and of power by 44.2% and 7.0%, respectively for soleus and gastrocnemius in simulation.Clinical Relevance-The proposed Unpowered Ankle-Foot Exoskeleton can both reduce muscle forces and powers. Hence, it can be used to assist walking of the elderly, others with neurocognitive disorders or leg diseases.

The occurrence of excessive ammonium in groundwater threatens human and aquatic ecosystem health across many places worldwide. As the fate of ammonium in groundwater systems is often affected by a complex mixture of transport and biogeochemical transformation processes, identifying the sources of groundwater ammonium is an important prerequisite for planning effective mitigation strategies. Elevated ammonium was found in both a shallow and an underlying deep groundwater system in an alluvial aquifer system beneath an agricultural area in the central Yangtze River Basin, China. In this study we develop and apply a novel, indirect approach, which couples the random forest classification (RFC) of machine learning method and fluorescence excitation-emission matrices with parallel factor analysis (EEM-PARAFAC), to distinguish multiple sources of ammonium in a multi-layer aquifer. EEM-PARAFAC was applied to provide insights into potential ammonium sources as well as the carbon and nitrogen cycling processes affecting ammonium fate. Specifically, RFC was used to unravel the different key factors controlling the high levels of ammonium prevailing in the shallow and deep aquifer sections, respectively. Our results reveal that high concentrations of ammonium in the shallow groundwater system primarily originate from anthropogenic sources, before being modulated by intensive microbially mediated nitrogen transformation processes such as nitrification, denitrification and dissimilatory nitrate reduction to ammonium (DNRA). By contrast, the linkage between high concentrations of ammonium and decomposition of soil organic matter, which ubiquitously contained nitrogen, suggested that mineralization of soil organic nitrogen compounds is the primary mechanism for the enrichment of ammonium in deeper groundwaters.

Iodine is an essential micronutrient in the human diet and an appropriate human iodine intake level is important for population health. Excessive iodine intake is often associated with high iodine groundwater which serves as an important drinking water source in many regions. This study aims to identify the source and key hydrogeochemical processes for iodine accumulation and mobility in the groundwaters of the Northern Jiangsu Yishusi Plain. Combined hydrogeochemical and statistical analyses, specifically random forest modeling and factor analysis, were used to explore the mechanisms affecting the spatial distribution of iodine. The concentration of iodine in the investigated groundwaters was found to vary widely and to range between 4.8 and 4750 μg/L, with 48.9% of the total samples (674) exceeding the threshold value of 100 μg/L for toxic exposure, as defined by the Chinese high‑iodine standard guideline. High iodine concentrations are shown to mainly occur in the marine plain and the shallow aquifer associated with the floodplains of the Old Yellow River. The marine or lagoons-facies sediments were identified as the most plausible iodine source. In addition, mixing of groundwater with paleo-seawater might also have played a role in the coastal area. In contrast, the flood sediments of the Old Yellow River are shown to be an unlikely source. However, they serve as a cover layer that favored the development of reducing hydrogeochemical conditions that can trigger iodine mobilization via the reductive dissolution of iron oxides and the degradation of organic matter. Slow groundwater flow rates also appear to favor iodine release from sediments.

Several water-solubilized versions of the zinc ionophore 1-hydroxypyridine-2-thione (ZnHPT), synthesized as part of the present study, have been found both to increase the intracellular concentrations of free zinc and to produce an antiproliferative activity in exponential phase A549 human lung cancer cultures. Gene expression profiles of A549 cultures treated with one of these water-soluble zinc ionophores, PCI-5002, reveal the activation of stress response pathways under the control of metal-responsive transcription factor 1 (MTF-1), hypoxia-inducible transcription factor 1 (HIF-1), and heat shock transcription factors. Additional oxidative stress response and apoptotic pathways were activated in cultures grown in zinc-supplemented media. We also show that these water-soluble zinc ionophores can be given to mice at 100 μmol/kg (300 μmol/m2) with no observable toxicity and inhibit the growth of A549 lung and PC3 prostate cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice 4 h after treatment confirmed the in vivo activation of MTF-1–responsive genes. Overall, we propose that water-solubilized zinc ionophores represent a potential new class of anticancer agents. [Cancer Res 2008;68(13):5318–25]