Targeting S1PRs as a Therapeutic Strategy for Inflammatory Bone Loss Diseases—Beyond Regulating S1P Signaling

As G protein coupled receptors, sphingosine-1-phosphate receptors (S1PRs) have recently gained attention for their role in modulating inflammatory bone loss diseases. Notably, in murine studies inhibiting S1PR2 by its specific inhibitor, JTE013, alleviated osteoporosis induced by RANKL and attenuated periodontal alveolar bone loss induced by oral bacterial inflammation. Treatment with a multiple S1PRs modulator, FTY720, also suppressed ovariectomy-induced osteoporosis, collagen or adjuvant-induced arthritis, and apical periodontitis in mice. However, most previous studies and reviews have focused mainly on how S1PRs manipulate S1P signaling pathways, subsequently affecting various diseases. In this review, we summarize the underlying mechanisms associated with JTE013 and FTY720 in modulating inflammatory cytokine release, cell chemotaxis, and osteoclastogenesis, subsequently influencing inflammatory bone loss diseases. Studies from our group and from other labs indicate that S1PRs not only control S1P signaling, they also regulate signaling pathways induced by other stimuli, including bacteria, lipopolysaccharide (LPS), bile acid, receptor activator of nuclear factor κB ligand (RANKL), IL-6, and vitamin D. JTE013 and FTY720 alleviate inflammatory bone loss by decreasing the production of inflammatory cytokines and chemokines, reducing chemotaxis of inflammatory cells from blood circulation to bone and soft tissues, and suppressing RANKL-induced osteoclast formation.     

DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Hydraulic reactivity and cement formation of baghdadite

In this study, the hydraulic reactivity and cement formation of baghdadite (Ca₃ZrSi₂O₉) was investigated. The material was synthesized by sintering a mixture of CaCO₃, SiO₂, and ZrO₂ and then mechanically activated using a planetary mill. This leads to a decrease in particle and crystallite size and a partial amorphization of baghdadite as shown by X-ray powder diffraction (XRD) and laser diffraction measurements. Baghdadite cements were formed by the addition of water at a powder to liquid ratio of 2.0 g/ml. Maximum compressive strengths were found to be ~2 MPa after 3-day setting for a 24-h ground material. Inductively coupled plasma mass spectrometry (ICP-MS) measurements showed an incongruent dissolution profile of set cements with a preferred dissolution of calcium and only marginal release of zirconium ions. Cement formation occurs under alkaline conditions, whereas the unground raw powder leads to a pH of 11.9 during setting, while prolonged grinding increased pH values to approximately 12.3.     

Spatiotemporal Magnetocaloric Microenvironment for Guiding the Fate of Biodegradable Polymer Implants

The degradation behavior of implants is significantly important for bone repair. However, it is still unprocurable to spatiotemporally regulate the degradation of the implants to match bone ingrowth. In this paper, a magneto-controlled biodegradation model is established to explore the degradation behavior of magnetic scaffolds in a magnetothermal microenvironment generated by an alternating magnetic field (AMF). The results demonstrate that the scaffolds can be heated by magnetic nanoparticles (NPs) under AMF, which dramatically accelerated scaffold degradation. Especially, magnetic NPs modified by oleic acid with a better interface compatibility exhibit a greater heating efficiency to further facilitate the degradation. Furthermore, the molecular dynamics simulations reveal that the enhanced motion correlation between magnetic NPs and polymer matrix can accelerate the energy transfer. As a proof-of-concept, the feasibility of magneto-controlled degradation for implants is demonstrated, and an optimizing strategy for better heating efficiency of nanomaterials is provided, which may have great instructive significance for clinical medicine.     

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.     

深部松软煤层钻孔孔周煤体变形产渣特征研究

针对煤矿井下高瓦斯软煤顺层长钻孔排渣困难、成孔率低、施工困难等问题,通过数值模拟实验研究了井下深部软煤体变形破坏特征,分析了顺层长钻孔孔周松软煤体变形特征及应力变化,以揭示顺层长钻孔孔周松软煤体变形产渣规律。研究表明:深部高瓦斯软煤顺层钻孔孔周煤体的应力平衡临界条件破坏后将发生大体积突然垮落;钻孔水平最大变形位移为1.22mm,垂直方向最大变形位移为10.7mm;径向孔周煤体垂向变形呈现逐渐减小趋势,且垂向变形明显大于钻孔水平变形。在水平方向上,钻孔孔周煤体应力分布呈现先增大再逐渐减小的变化规律,径向距离对水平应力分布的影响逐渐减小;随着径向距离的增加,钻孔孔周煤体应力分布逐渐降低,钻孔孔壁处煤体的应力出现最大值,且垂直方向处应力值最大。     

炼油废白土在水泥厂燃煤自备电厂中再利用的实践

本项目主要研究和实现了工业废白土在BAYAH燃煤自备电厂中的再利用,实现变废为宝,减少了环境污染,同时为企业创造了一定的经济效益。针对废白土的特性,对燃料输送系统给煤机、皮带机、煤仓、下料溜子和排渣系统进行了改造。通过修改操作规程消除废白土对锅炉运行的影响。     

液压支架快速撤除技术研究应用

新汶矿业集团经过探索和实践,研究运用了差异互补式全掩护支护技术、掩护支架自牵引联动装置工艺、矿车运输、滑移运输多用轨道、自动找正装车平台、液控调整装置等新技术、新工艺,做到了液压支架综合流程快速回撤,实现了高效化、连贯化安全回撤,取得了良好的经济效益。     

智能化救援监控系统在煤矿安全生产中的应用

针对煤矿发生事故后传统救援监控系统无法实时对井下人员进行动态定位，导致矿井救援盲目性大、救援效率差、救援难度大等技术难题，为了进一步提高煤矿救援效率，通过技术研究，设计了一套以通信基站为核心的智能化救援监控系统，分析了该系统结构组成、工作原理，通过在担水沟煤矿井下实际应用效果来看，智能化救援监控系统对人员定位精准度达95%，实现人员动态位置三维成像，救援效率提高至80%以上，有效缩短了煤矿事故救援时间，取得了显著应用成效。