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Objectives: To compare the effects of signaling-selective parathyroid hormone analogs [G1, R19]hPTH(1–28) [GR(1–28)] and [G1, R19]hPTH(1–34) [GR(1–34)] on osteoporotic osteocyte apoptosis, and to explore the mechanism of the anti-osteoporotic difference. Methods: The osteoporosis model was established in eighty adult female C57BL/6 mice aged 12 weeks. The mice were subcutaneously administered with GR(1–28) and GR(1–34) 5 days per week for 8 weeks. Bilateral femur samples were collected at 4 and 8 weeks, and micro-computed tomography (CT), H&E staining and immunohistochemical staining analyses were performed. Results: From micro-CT analysis, GR(1–34) increased proximal femoral bone mineral density (BMD) and relative bone volume (BV/TV), which was higher than GR(1–28) did. In addition, more trabecular number (Tb.N), thinner trabecular thickness (Tb.Th) and wider trabecular separation (Tb.Sp) were measured at week 8 using GR(1–34). From H&E and immunohistochemical staining, a stronger apoptosis inhibition was induced by GR(1–34) with more Bcl-2 secretion but less Bax expression, as opposed to GR(1–28). Conclusions: GR(1–34) shows better anti-osteoporotic effects than GR(1–28), which appears to be attributed to the activation of the PLC-independent PKC signaling pathway triggered by the former, inhibiting osteocyte apoptosis through up-regulation of Bcl-2 and down-regulation of Bax to increase bone mass and improving trabecular bone microstructure to enhance bone quality by reducing trabecular number, increasing trabecular thickness and trabecular space.

Quantum Private Information Retrieval (QPIR) allows a user (Alice) to retrieve a database item from the database owned by the database holder (Bob) in such a way that Alice can query only the database item she wants, but cannot get other items, and Bob does not know which item Alice queries. However, the real quantum channel between Alice and Bob is noisy, and the noise may result in not only the chance that Alice obtains a false item, but also that both parties may cheat by camouflaging themselves with noise. In this paper, we use the decoherence-free subspace (DFS) for QPIR, which we call DFS-QPIR. The DFS-QPIR protocol removes the effect of the channel noise on the errors in the retrieved item so that two parties cannot cheat by replacing the noisy channel with a noiseless one. It can work over a collective noisy channel while retaining high reliability, database security and user privacy simultaneously. While only the collective unitary noise is taken into account, the proposed DFS-QPIR protocol can be straightforwardly extended to more general collective noise channel.

Recent evidence indicates that the abnormal differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) plays a pivotal role in the pathogenesis of osteoporosis. LncRNA SNHG1 has been found to be associated with the differentiation ability of BMSCs. In this study, we aimed to elucidate the role of lncRNA SNHG1 and its associated pathway on the differentiation of BMSCs in osteoporosis. Mice that underwent bilateral ovariectomy (OVX) were used as models of osteoporosis. Induced osteogenic or adipogenic differentiation was performed in mouse BMSCs. Compared to sham animals, lncRNA SNHG1 expression was upregulated in OVX mice. Also, the in vitro expression of SNHG1 was increased in adipogenic BMSCs but decreased in osteogenic BMSCs. Moreover, overexpression of SNHG1 enhanced the adipogenic capacity of BMSCs but inhibited their osteogenic capacity as determined by oil red O, alizarin red, and alkaline phosphatase staining, while silencing of SNHG1 led to the opposite results. LncRNA SNHG1 interacting with the RNA‐binding polypyrimidine tract‐binding protein 1 (PTBP1) promoted osteoprotegerin (Opg) methylation and suppressed Opg expression via mediating DNA methyltransferase (DNMT) 1. Furthermore, Opg was showed to regulate BMSC differentiation. Knockdown of SNHG1 decreased the expressions of adipogenic related genes but increased that of osteogenic related genes. However, the knockdown of Opg partially reversed those effects. In summary, lncRNA SNHG1 upregulated the expression of DNMT1 via interacting with PTBP1, resulting in Opg hypermethylation and decreased Opg expression, which in turn enhanced BMSC adipogenic differentiation and contributed to osteoporosis.

Background We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. Methods The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of β-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro. Results SNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/β-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs. Conclusions Collectively, SP1-induced SNHG1 modulated SFRP1/Wnt/β-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis. Graphic abstract

The hydrodynamic coupling of inverted flexible flags in side-by-side, left triangular and right triangular configurations in a uniform flow is investigated numerically. Various arrangements can be characterized by the lateral and longitudinal gaps, i.e., H and G, respectively. For the side-by-side configurations, three typical modes are identified in flapping region, i.e., in-phase quasi out-of-phase (QOP) and out-of-phase (OP) modes, corresponding to 2P, irregular and 4(P + S) wake patterns, respectively. Further analysis on the mean drag coefficient (Cd̄) and bending energy (Eb̄) indicates that the side-by-side flags can not harvest more bending energy from surrounding flows than the isolated one, except for a narrow range of H ∈ (1.8, 2.5). Moreover, an additional inverted flag is placed in front or rear of the side-by-side flags to explore possible favorable arrangements for bending energy enhancement. Three typical modes have been identified in the H − G planes for both left and right triangular configurations, i.e., the regular-coupled (RC), irregular-coupled (IC) and decoupled (DC) modes, respectively. For left triangular configurations, the overall system may experience significant performance enhancement in some favorable configurations, corresponding to harvest enhancement region (HER) in the G − H plane; For the case in HER, especially, the Eb̄ of the rear flag may increase by up to 30% than isolated flag. While for right triangular configurations, no HER is observed. The unsteady flow characteristics are further explored to reveal the mechanism of hydrodynamic coupling in system. The present study may shed some light on understanding the dynamics of this multi-flag system.