Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to ...recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.
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This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.
Senescence and altered differentiation potential of bone marrow stromal cells (BMSCs) lead to age‐related bone loss. As an important posttranscriptional regulatory pathway, alternative splicing (AS) ...regulates the diversity of gene expression and has been linked to induction of cellular senescence. However, the role of splicing factors in BMSCs during aging remains poorly defined. Herein, we found that the expression of the splicing factor Y‐box binding protein 1 (YBX1) in BMSCs decreased with aging in mice and humans. YBX1 deficiency resulted in mis‐splicing in genes linked to BMSC osteogenic differentiation and senescence, such as Fn1, Nrp2, Sirt2, Sp7, and Spp1, thus contributing to BMSC senescence and differentiation shift during aging. Deletion of Ybx1 in BMSCs accelerated bone loss in mice, while its overexpression stimulated bone formation. Finally, we identified a small compound, sciadopitysin, which attenuated the degradation of YBX1 and bone loss in old mice. Our study demonstrated that YBX1 governs cell fate of BMSCs via fine control of RNA splicing and provides a potential therapeutic target for age‐related osteoporosis.
Synopsis
Alternative splicing has been shown to regulate cellular senescence and differentiation. This study links the reduced expression of the splicing regulator YBX1 in aging bone marrow stromal cells to senescence and aging‐related bone loss.
The expression level of YBX1 in BMSCs decreases during aging.
Ybx1 overexpression in BMSCs stimulates bone formation, while its deletion accelerates bone loss.
YBX1 suppresses BMSC senescence and modulates BMSC differentiation by controlling RNA splicing.
The small compound sciadopitysin attenuates YBX1 degradation and bone loss in old mice.
Reduced expression of YBX1 in aging bone marrow stromal cells induces their senescence and bone loss due to mRNA mis‐splicing.
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31
Emcn
), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31
Emcn
vessels decrease during ...ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31
Emcn
endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31
Emcn
vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31
Emcn
vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31
Emcn
vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis.
We first report three reliable analytical expressions of the entropy, enthalpy and Gibbs free energy of carbon dioxide (CO2) and perform predictions of these three thermodynamic quantities on the ...basis of the proposed analytical expressions and in terms of experimental values of five molecular constants for CO2. The average relative deviations of the calculated values from the National Institute of Standards and Technology database over the temperature range from 300 to 6000 K are merely 0.053, 0.95, and 0.070%, respectively, for the entropy, enthalpy, and Gibbs free energy. The present predictive expressions are away from the utilization of plenty of experimental spectroscopy data and are applicable to treat CO2 capture and storage processes.
The diamond/ZnSe/ITO composite film (DZSCF) electroluminescence (EL) device was deposited on n-type heavily doped silicon substrate by microwave plasma chemical vapor deposition technique and vacuum ...electron beam vapor deposition technique. Its composition, microstructure, current-voltage characteristic and EL characteristic were characterized with a series of corresponding detection equipment. The experimental results show that the device can emit strong white light at a forward applied voltage of 240 V, and its CIE coordinates (0.361,0.334) show that its white light purity is higher and its corresponding color temperature is lower(4271 K). The EL spectra of the device show two broad peaks in the blue-green region (central wavelength at 496 nm) and the red region (central wavelength at 660 nm), respectively. In addition, the device also exhibits obvious rectification characteristics. The corresponding experimental results are explained reasonably.
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•A diamond/ZnSe composite film EL device was made. The device can emit strong white light visible to the naked eye.•The electron acceleration effect of diamond layer effectively improve the EL intensity of ZnSe layer.•This study provides a new possible way to achieve high luminance white electroluminescent based on diamond thin film.
High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA
that is associated with ...HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous
individuals had higher bone density compared with subjects with WT
Mutant
increased the formation of the CD31
Emcn
endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant
directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of
in endothelial cells showed a high abundance of CD31
Emcn
vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31
Emcn
vessels and bone formation. Our findings revealed a specific mutation in lncRNA
that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.
•Changes in hydro-geological environment (HGE) due to water inflow were investigated in a case.•A water inrush model considering the nonlinear flow and particle erosion was developed.•The potential ...water inflows and the HGE changes were evaluated for future excavations.•The practical implications were discussed with field and numerical results.
Groundwater inflow during tunnel excavation and its influences on the hydro-geological environment (HGE) are vital to green construction and environmental sustainability. To evaluate these issues in completely weathered granite formation, a water inrush event occurred in Junchang tunnel is introduced to investigate the changes in HGE including groundwater level, ground surface settlement, surface fractures as well as the tunnel settlement. Then, a seepage-erosion coupling model is developed to predict water inrush and its influences on the HGE changes. This model can describe the characteristics of nonlinear seepage and particle erosion for water inrush and its effectiveness is verified by the field results. Using this model, the potential water inrush and the changes in HGE are evaluated for future excavation in various high-risk positions. Consequently, the real-time water inrush process, the HGE changes and the practical implications are discussed with the field and numerical results. The main research findings include: (1) the evolution direction, mutation time and the volume of the water inrush, and (2) the influenced region, evolution time and the extend of the changes in HGE. These findings can provide references for the early warning, monitoring and prevention for future constructions.
A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone ...tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.
Diamond/boron/diamond/SrTiO3 composite film (BDDSCF) electroluminescent (EL) devices were deposited by microwave plasma chemical vapor deposition (MPCVD) technology and vacuum electron beam vapor ...deposition (EBVD) technology. The samples were characterized by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and energy dispersive spectroscopy (EDXS). The current-voltage (I–V) characteristic of the sample was measured by an adjustable direct current power supply. The EL spectra of the samples obviously exhibit three emission peaks, which are centered at 440 nm (blue area), 592 nm (yellow area) and 736 nm (red area). In the indoor environment, it can be observed by the naked eye that the surface of the sample will emit uniform and high brightness white light. The blue peak is from the recombination of the conduction band electron in SrTiO3 film and the quasi-acceptor (trapped hole) associated with oxygen vacancy, the yellow peak is caused by the self-trapping exciton (STE) recombination caused by oxygen vacancies in SrTiO3, and the red peak is attributed to the silicon impurity centers or carbon neutral vacancy in diamond films.
•Diamond/boron/diamond/SrTiO3 composite film high-brightness white light-emitting device was made for the first time.•The emission peaks in EL spectrum were found at 436 nm, 592 nm and 708 nm, respectively.•This study provides a promising new idea for the development of other non-GaN based white electroluminescence.
Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare ...establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.
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