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Although platelet-rich plasma-derived exosomes (PRP-Exos) hold significant repair potential, their efficacy in treating rotator cuff tear (RCT) remains unknown. In light of the potential for clinical translation of fibrin gel and PRP-Exos, we evaluated their combined impact on RCT healing and explored suitable gel implantation techniques. In vitro experiments demonstrated that PRP-Exos effectively enhanced key phenotypes changes in tendon stem/progenitor cells. Multi-modality imaging, including conventional ultrasound, shear wave elastography ultrasound, and micro-computed tomography, and histopathological assessments were performed to collectively evaluate the regenerative effects on RCT. The regenerated tendons exhibited a well-ordered structure, while bone and cartilage regeneration were significantly improved. PRP-Exos participated in the healing process of RCT. In-situ gelation of fibrin gel-encapsulated PRP-Exos at the bone-tendon interface during surgery proved to be a feasible gel implantation method that benefits the healing outcome. Comprehensive multi-modality postoperative evaluations were necessary, providing a reliable foundation for post-injury repair. In this study, the authors have investigated if the implantation of fibrin gel loaded with platelet-rich plasma-derived exosomes is a feasible strategy to treat rotator cuff injuries. In fact, this strategy proved to promote tendon repair and healing outcomes in a rabbit model of rotator cuff injury. [ABSTRACT FROM AUTHOR]

Aging of mesenchymal stem cells(MSCs) has been widely reported to be strongly associated with aging-related diseases, including osteoporosis (OP). In particular, the beneficial functions of mesenchymal stem cells decline with age, limiting their therapeutic efficacy in age-related bone loss diseases. Therefore, how to improve mesenchymal stem cell aging to treat age-related bone loss is the current research focus. However, the underlying mechanism remains unclear. In this study, protein phosphatase 3, regulatory subunit B, alpha isoform, calcineurin B, type I (PPP3R1) was found to accelerate the senescence of mesenchymal stem cells, resulting in reduced osteogenic differentiation and enhanced adipogenic differentiation in vitro. Mechanistically, PPP3R1 induces changes in membrane potential to promote cellular senescence by polarizing to depolarizing, increasing Ca2+ influx and activating downstream NFAT/ATF3/p53 signaling. In conclusion, the results identify a novel pathway of mesenchymal stem cell aging that may lead to novel therapeutic approaches for age-related bone loss. [ABSTRACT FROM AUTHOR]

Inventory is the core link of enterprise operation and an essential resource for enterprises to occupy the market. Therefore, optimizing the control and management of inventory is a necessary measure for enterprises to maintain their core competitiveness. However, at present, the optimization of the enterprise's inventory is basically still at the single inventory level, which seriously shortens the life cycle of the enterprise's products and reduces the speed of the enterprise's capital flow. Digital supply chain is the digitization of traditional supply chain services, which can change the traditional thinking of inventory control and management, break down the barriers between enterprises and modern logistics, and build a complete management system for enterprises. Smart logistics is a product of the new era, and it is also a product of the development of the digital supply chain. To this end, this paper proposes an inventory optimization algorithm based on digital supply chain and smart logistics. The algorithm is optimized on the basis of the original inventory optimization scheme, so that the improved algorithm can be more suitable for actual inventory management needs. The experimental results of this paper show that the improved new inventory optimization algorithm improves the comprehensive benefit by 39.1% on the original basis, which can effectively reduce the error in the actual use process. [ABSTRACT FROM AUTHOR]

In multi-access edge computing systems with energy harvesting (MEC-EH), the mobile devices are empowered with unstable energy harvested from renewable energy sources. To prolong the life of mobile devices, as many computation-intensive tasks as possible should be offloaded to the MEC server. However, when the system states of mobile device and MEC server are unstable, e.g. poor communication channel conditions, a great number of tasks will be executed locally, leading to a long execution time. Even worse, some tasks may be dropped due to low energy levels. To address this problem, in this paper, we propose a multi-relay assisted computation offloading framework for MEC-EH systems. In this framework, a computation task can be executed by offloading to the MEC server with the help of multiple relay nodes, such as the neighboring nodes. We introduce execution cost as a performance metric to incorporate both the task execution time and task failure. We then develop a low-complexity online algorithm, namely MRACO algorithm, to minimize the average execution cost. MRACO algorithm can select the optimal execution strategy for each task from (1) executing the task locally, (2) offloading it to the MEC server directly, (3) offloading it to the MEC server with the help of the most suitable neighboring nodes, and (4) simply dropping it. Moreover, we also develop an algorithm for selecting the suitable neighboring devices to act as relays and determining the optimal task splitting ratio between them. Finally, performance evaluation shows that the proposed MRACO algorithm greatly outperforms the benchmarks in terms of both average execution time and task drop rate. [ABSTRACT FROM AUTHOR]

Introduction: Long noncoding RNAs (lncRNAs) play an important role in the origination and progression of hepatocellular carcinoma (HCC). However, the biological function of the long intergenic non-protein-coding RNA, LINC01296, in HCC remains unknown. Methods: Here, we observed an increase in the expression levels of LINC01296 in HCC tissues and cell lines using reverse transcription quantitative PCR; these data were consistent with that obtained from The Cancer Genome Atlas database. Results: A higher expression level was correlated with higher alpha fetoprotein levels, a larger tumor size, an advanced TNM stage, and a poorer overall survival rate. Upregulation of LINC01296 promoted the proliferation, migration, and invasion of HCC cells. Improvement of cell migration and invasion attributable to the overexpression of LINC01296 was related to an increase in epithelial–mesenchymal transition (EMT). Mechanistically, miR-122-5P can bind to LINC01296 and decrease its oncogenic effect. Conclusion: Collectively, the results of this study revealed that LINC01296 is a tumor promoter that can promote the migration and invasion of HCC cells through EMT, while miR-122-5P is involved in the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Color-tunable blue to bluish white-emitting Ce 3+ /Dy 3+ co-doped GdOBr phosphors have been synthesized by the conventional solid-state method. The phase structures, luminescent properties and energy transfer process were discussed in detail. Broad-band absorption originating from the f-d transition of Ce 3+ can be found for the as-prepared GdOBr:Ce 3+ ,Dy 3+ phosphor, and color-tunable blue to bluish white emission can be realized owing to the energy transfer between Ce 3+ and Dy 3+ . The energy transfer mechanism is demonstrated to be the dipole–dipole process. The energy transfer efficiency increases with increasing Dy 3+ concentrations. The results indicate that Ce 3+ /Dy 3+ -activated GdOBr phosphors may be potential for phosphor-converted white-light UV-LEDs. [ABSTRACT FROM AUTHOR]

Glycogen synthase kinase 3 β ( GSK3 β) is a multifunctional serine/threonine protein kinase that is involved in several biological processes including insulin and Wnt signaling pathways. GSK3 β can be phosphorylated by the protein kinase B ( PKB). The mutations of Arg4 and Arg6 to alanine at N-terminal GSK3 β have been reported to impair its ability to autophosphorylate at Ser9. Despite the extensive experimental observations, the detailed mechanism for the auto-inhibition of GSK3 β has not been rationalized at the molecular level. In this study, we have demonstrated the structural consequences of GSK3 β R4 A and R6 A mutations and the atomic changes that influenced the loss of PKB-binding affinity. Molecular dynamics simulation results suggested significant loss in atomic contacts in the R4 A and R6 A mutant systems compared to the wild-type system. Furthermore, we observed many notable changes (such as conformation, residues motions, hydrogen bonds, and binding free energy) in the mutated GSK3 β- PKB complexes. Loss of binding affinity in the mutated systems rendered the decrease in GSK3 β phosphorylation, which, in turn, impaired the auto-inhibition of GSK3 β. The significant outcomes obtained from this study can explain the auto-inhibition of GSK3 β and maybe facilitate type 2 diabetes mellitus researches and in developing the potent drug therapies. [ABSTRACT FROM AUTHOR]

Abstract: The miR-92a family, including miR-25, miR-92a-1, miR-92a-2 and miR-363, arises from three different paralog clusters miR-17-92, miR-106a-363, and miR-106b-25 that are highly conservative in the process of evolution, and it was thought as a group of microRNAs (miRNAs) correlated with endothelial cells. Aberrant expression of miR-92a family was detected in multiple cancers, and the disturbance of miR-92a family was related with tumorigenesis and tumor development. In this review, the progress on the relationship between miR-92a family and their target genes and malignant tumors will be summarized. [Copyright &y& Elsevier]

Abstract: MicroRNAs (miRNAs) are a class of endogenous, non-coding, 18–24 nucleotide length single-strand RNAs that could modulate gene expression at post-transcriptional level. Previous studies have shown that miR-128 enriched in the brain plays an important role in the development of nervous system and the maintenance of normal physical functions. Aberrant expression of miR-128 has been detected in many types of human tumors and its validated target genes are involved in cancer-related biological processes such as cell proliferation, differentiation and apoptosis. In this review, we will summarize the roles of miR-128 and its target genes in tumorigenesis and metastasis. [Copyright &y& Elsevier]

Background: Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. Methods: In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. Results: Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. Conclusions: The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury (PNI) remains a severe clinical problem with debilitating consequences. Mesenchymal stem cell (MSC)-based therapy is promising, but the problems of poor engraftment and insufficient neurotrophic effects need to be overcome. Herein, we isolated platelet-rich plasma-derived exosomes (PRP-Exos), which contain abundant bioactive molecules, and investigated their potential to increase the regenerative capacity of MSCs. We observed that PRP-Exos significantly increased MSC proliferation, viability, and mobility, decreased MSC apoptosis under stress, maintained MSC stemness, and attenuated MSC senescence. In vivo, PRP-Exo-treated MSCs (pExo-MSCs) exhibited an increased retention rate and heightened therapeutic efficacy, as indicated by increased axonal regeneration, remyelination, and recovery of neurological function in a PNI model. In vitro, pExo-MSCs coculture promoted Schwann cell proliferation and dorsal root ganglion axon growth. Moreover, the increased neurotrophic behaviour of pExo-MSCs was mediated by trophic factors, particularly glia-derived neurotrophic factor (GDNF), and PRP-Exos activated the PI3K/Akt signalling pathway in MSCs, leading to the observed phenotypes. These findings demonstrate that PRP-Exos may be novel agents for increasing the ability of MSCs to promote neural repair and regeneration in patients with PNI. [Display omitted] • PRP-Exos enhance the viability, survival, stemness, and neurotrophic paracrine properties of MSCs. • Transplantation of pExo-MSCs leads to improved functional recovery of PNI by promoting axonal regeneration and remyelination. • GDNF plays a crucial role in mediating the superior neurotrophic function of pExo-MSCs. • PRP-Exos enhance the neurotrophic properties of MSCs by activating the PI3K/Akt signalling pathway. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidences indicate that circRNAs play important roles in the progression and chemoresistance of human cancers. The present study is designated for researching the roles of circ_0003418 in hepatocellular carcinoma (HCC). Methods: We detected the expression profile of circ_0003418 in human HCC tissues and cell lines by quantitative real-time-PCR assays. CCK-8 assay, transwell migration assay, transwell invasion assay and drug-sensitivity analysis were carried out to estimate the effects of circ_0003418 on HCC cells' proliferation, migration, invasion and resistance to cisplatin, respectively. Mouse xenograft model was conducted to monitor the role of circ_0003418 in cisplatin resistance in vivo. Western blotting was performed to explore the changes of the Wnt/β-catenin pathway after knockdown of circ_0003418. The rescue experiment was carried out to explore circ_0003418-activated biological functions through Wnt/β-catenin pathway. Results: The expression level of circ_0003418 was downregulated in HCC tissues and cell lines, and the level correlated with tumor size, TNM stage and HBsAg level in HCC patients. circ_0003418 knockdown promoted HCC cells' proliferation, migration, and invasion. Additionally, suppression of circ_0003418 enhanced cisplatin resistance of HCC cells in vivo and vitro. Knockdown of circ_0003418 activated the Wnt/β-catenin signalling pathway in HCC cells. The effect of circ-0003418 on sensitivity of HCC cells to cisplatin was reversed after inhibition of Wnt/β-catenin pathway. Conclusion: circ-0003418 exerts an antitumorigenic role in HCC and advances the sensitivity of HCC cells to cisplatin by restraining the Wnt/β-catenin pathway. Thus, circ-0003418 may represent a novel biomarker and provide us a new strategy for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Bone formation is critically needed in orthopedic clinical practice. We found that, bone morphogenetic protein-7 (BMP-7) gene expression was significantly increased in fractured mice, which activates canonical Wnt signaling exclusively in osteocytes. Wnt and BMP signaling appear to exhibit synergistic or antagonistic effects in different kinds of cells. However, the communication between Wnt/β-catenin signaling and BMP signaling in osteocytes is almost unknown. Our study verified in vitro that BMP-7 expression was significantly increased when Wnt signaling was activated in osteocytes. Next, BMP-7 in osteocytes was overexpressed using an adenovirus, the osteogenesis of bone marrow stem cells (BMSCs) was enhanced, when cocultured with osteocytes. On the contrary, BMP-7 in osteocytes was silenced using an adenovirus, the osteogenesis of bone marrow stem cells (BMSCs) was weakened. In addition, the osteogenesis of BMSCs was no longer promoted by Wnt-activated osteocytes when BMP-7 was silenced. Therefore, the results showed that BMP-7 mediated the anabolic actions of Wnt/β-catenin signaling in osteocytes. Our study provides new evidence for the clinical application of BMP-7-overexpressed osteocytes. [ABSTRACT FROM AUTHOR]

Background: Tumor metastasis is a finely-tuned pathological process coupled to metabolic reprogramming that includes both glutamine and glucose. The solute carrier SLC38A3, a member of amino acid/polyamine/organocation (APC) superfamily, is an l-glutamine transporter. It is not clear whether SLC38A3 involves the metastasis of NSCLC (non small cell lung cancer).Methods: The scratch test and transwell assay were used to determine the ability of NSCLC to migrate. Cellular amino acids content was determined by mass spectrometry. The cellular response to glutamine/histidine deficiency was evaluated in A549 cells. The expression of SLC38A3 was assayed in clinical NSCLC and paratumor tissues by histoimmunochemistry staining. A nude mouse model of NSCLC metastasis was developed by tail vein injection of tumor cells.Results: SLC38A3 was upregulated in metastatic NSCLC cells and its expression was correlated with prognosis of NSCLC patients. SLC38A3 overexpression promoted epithelial - mesenchymal transition (EMT) and migration of HCC827 and A549 human lung adenocarcinoma cells, and accelerated tumor metastasis in mice. We found that SLC38A3 decreased the cellular concentrations of glutamine and histidine, and the deficiency of glutamine or histidine activated PDK1/AKT signaling that in turn, triggered NSCLC metastasis.Conclusions: SLC38A3 activated PDK1/AKT signaling and promoted metastasis of NSCLC through regulating glutamine and histidine transport, suggesting SLC38A3 as a potential therapeutic target for treatment of NSCLC. [ABSTRACT FROM AUTHOR]

miRNA-125 family, which is a highly conserved miRNA family throughout evolution, is consist of miRNA-125a-3p, miRNA-125a-5p, miRNA-125b-1 and miRNA-125b-2.The aberrant expression of miR-125 familyis tightly related to tumorigenesis and tumor development. The downstream targets of miRNA-125 include transcription factors like STAT3, cytokines like IL-6 and TGF-β, tumor suppressing protein p53, pro-apoptotic protein Bak1 and RNA binding protein HuR et al. Through regulating these downstream targets miR-125 family is involved in regulating tumorigenesis and tumor development. Nowadays, miR-125b have already became a putative and valuable biomarker for cancer diagnosis, treatment and prognosis. In this review, we mainly summarize the dual function of miRNA-125 family in suppression and promotion of cancer cells and further elaborate its regulatory mechanisms from four facets, proliferation, apoptosis, invasion or metastasis and immune response. [ABSTRACT FROM AUTHOR]

RbBaPO4:0.03Eu2+ (I), NaCaPO4:0.01Eu2+ (II), and CsMgPO4:0.07Eu2+ (III) phosphors are prepared by solid state reaction of stoichiometric mixtures of A2CO3 (A: Rb, Na, Cs), MCO3 (M: Ba, Ca), (MgCO3)4·Mg (OH)2·5H2O, (NH4)2HPO4, and Eu2O3 (alumina crucibles, CO atmosphere, 1150 °C, 3 h). [ABSTRACT FROM AUTHOR]

Emission-tunable phosphors Ca 9 La(PO 4 ) 5 (SiO 4 )F 2 :Ce 3+ ,Tb 3+ with apatite structure were synthesized by a solid-state reaction. The phase structure, photoluminescence (PL) properties, lifetimes and the PL thermal stability were investigated, respectively. The phosphor exhibited an asymmetric broad-band blue emission (Ce 3+ ) with peak at 403 nm and the line-type green emission with peak at 543 nm (Tb 3+ ). The varied color of the phosphors from blue to green can be achieved by properly tuning the relative ratio of Ce 3+ /Tb 3+ through the energy transfer from Ce 3+ to Tb 3+ ions. The critical distance was calculated to be 8.78 Å by using the concentration quenching method. When the temperature turned up to 150 °C, the emission intensity of Ca 9 La(PO 4 ) 5 (SiO 4 )F 2 :Ce 3+ ,Tb 3+ phosphor was 77% of its initial value at room temperature, which indicated the good thermal stability of the sample. All the properties indicate that the Ca 9 La(PO 4 ) 5 (SiO 4 )F 2 :Ce 3+ ,Tb 3+ phosphor has potential application of color-tunable w -LEDs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Novel Na0.60Ca0.40Sc0.60Mg0.40Si2O6:Eu2+,Mn2+ phosphors have been prepared. [•] Full-color white emission can be realized in the single host with different emission centers. [•] A white LED lamp was fabricated to demonstrate good luminescence properties. [ABSTRACT FROM AUTHOR]

• Aberrant expression of miR-26 can be detected in various kinds of malignant tumors. • The expression of miR-26 is regulated at four levels: gene amplification or LOH, SNP, transcriptional regulation, estrogen etc. • miR-26's validated target genes are involved in metabolism, proliferation, differentiation, apoptosis, invasion and metastasis of tumor cells. • miR-26 plays important roles in tumorigenesis and development. The microRNA-26 family, including miR-26a, miR-26b, miR-1297 and miR-4465, is a group of broadly conserved small RNAs with identical sequences at the seed region. The expression of miR-26 could be induced by hypoxia via a HIF-dependent mechanism, and up-regulated during multiple cell differentiation. Accumulating studies have demonstrated that miR-26 family members could be detected in many different kinds of tumors, and their validated target genes are involved in cell metabolism, proliferation, differentiation, apoptosis, invasion and metastasis. The expression of miR-26 might be a potentially valuable biomarker and a new target for cancer therapy. In this review, miR-26 family and its target genes in tumorigenesis and development will be summarized as follows. [ABSTRACT FROM AUTHOR]