Unexpectedly high thermoelectric performance of anisotropic Zr2Cl4monolayer.

Recently, the Hf2Cl4-type materials as functional materials have attracted broad interest because of their enormous potential in thermoelectric (TE) applications. However, relevant investigations are still scarce up to now. To explore the Hf2Cl4-type materials with excellent TE properties, we focus on the TE properties of Zr2Cl4monolayer and calculate the TE parameters based on first-principles calculations and Boltzmann transport equation. Although, as compared to some typical TE materials, it exhibits better heat transport and thus higher lattice thermal conductivity, the figure of merits (ZT) of both p-type and n-type Zr2Cl4reach an unexpectedly high value of 3.90 and 3.60, respectively, owing to the larger electrical conductivity and higher power factor. Additionally, owing to the prominent difference in electrical conductivity between thex- andy-direction, strong anisotropy inZTvalues is observed. Our study reveals that both n-type and p-type Zr2Cl4monolayers have the potential for future TE applications.

Paeoniflorin Ameliorates Hyperprolactinemia-Induced Inhibition of Osteoblastogenesis by Suppressing the NF-κB Signaling Pathway.

Hyperprolactinemia is a common endocrine disease in women of reproductive age. Research has shown that patients with hyperprolactinemia often have decreased bone mineral density and an increased risk of fractures. However, there is still a lack of effective treatments. Paeoniflorin, one of the primary bioactive components in peony, is widely used in traditional Chinese medicine. Research has shown that paeoniflorin promotes osteoblast differentiation. However, whether paeoniflorin plays a role in hyperprolactinemia-induced osteoblastogenesis inhibition is not yet clear. In this study, we investigated the effect of paeoniflorin on prolactin (PRL)-mediated inhibition of osteoblast function. Our results showed that prolactin significantly reduced the expression of alkaline phosphatase (ALP), Osterix, and runt-related transcription factor 2 (RUNX2) in MC3T3-E1 cells cultured in an osteoblast differentiation medium, suggesting that prolactin inhibited osteoblast function. After treatment with paeoniflorin (PF), the expression of these osteoblast markers was upregulated. In addition, our findings proved that paeoniflorin increased the absorbance values of ALP-positive cells and the areas of alizarin red S (ARS) deposition compared to those in the prolactin group, suggesting that paeoniflorin reversed the PRL-induced reduction in osteoblast differentiation. The PRL-induced activation of nuclear factor kappa B (NF-κB) was significantly reversed by paeoniflorin, indicating that paeoniflorin promoted osteoblast function by inhibiting the NF-κB signaling pathway. In summary, these results showed that paeoniflorin alleviated the inhibitory effect of prolactin on osteoblastogenesis by suppressing the NF-κB signaling pathway.

Activation of dopamine receptor D1 promotes osteogenic differentiation and reduces glucocorticoid-induced bone loss by upregulating the ERK1/2 signaling pathway.

BACKGROUND: The inhibition of osteogenic differentiation is a major factor in glucocorticoid-induced bone loss, but there is currently no effective treatment. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of the neuroendocrine system in bone metabolism has emerged, the precise effects of dopamine receptor signaling on osteoblastogenesis remain unknown. METHODS: In vitro, western blotting and immunofluorescence staining were used to observe the expression of dopamine receptors in MC3T3-E1 and BMSCs cells treated with dexamethasone (Dex). In addition, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining and western blotting were used to evaluate the effect of D1R activation on osteogenic differentiation in Dex-induced MC3T3-E1 cells via the ERK1/2 signaling pathway. In vivo, micro-CT and hematoxylin and eosin (H&E), toluidine blue and immunohistochemical staining were used to determine the effect of D1R activation on Dex-induced bone loss. RESULTS: We demonstrated that the trend in D1R but not D2-5R was consistent with that of osteogenic markers in the presence of Dex. We also demonstrated that the activation of D1R promoted Dex-induced osteogenic differentiation by activating the ERK1/2 pathway in vitro. We further demonstrated that a D1R agonist could reduce Dex-induced bone loss, while pretreatment with a D1R inhibitor blocked the effect of a D1R agonist in vivo. CONCLUSIONS: Activation of D1R promotes osteogenic differentiation and reduces Dex-induced bone loss by activating the ERK1/2 pathway. Hence, D1R could serve as a potential therapeutic target for glucocorticoid-induced osteoporosis.

Biomimetic cytomembrane nanovaccines prevent breast cancer development in the long term.

Cytomembrane cancer nanovaccines are considered a promising approach to induce tumor-specific immunity. Most of the currently developed nanovaccines, unfortunately, fail to study the underlying mechanism for cancer prevention and therapy, as well as immune memory establishment, with their long-term anti-tumor immunity remaining unknown. Here, we present a strategy to prepare biomimetic cytomembrane nanovaccines (named CCMP@R837) consisting of antigenic cancer cell membrane (CCM)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with imiquimod (R@837) as an adjuvant to activate the immune system. We found that our CCMP@R837 system enhanced bone-marrow-derived dendritic cell uptake and maturation, as well as increased anti-tumor response against breast cancer 4T1 cells in vitro. Moreover, an immune memory was established after three-time immunization with CCMP@R837 in BALB/c mice. The CCMP@R837-immunized BALB/c mice exhibited suppressed tumor growth and a long survival period (75% of mice lived longer than 50 days after tumor formation). This long-term anti-tumor immunity was achieved by increasing CD8+ T cells and decreasing regulatory T cells in the tumor while increasing effector memory T cells in the spleen. Overall, our platform demonstrates that CCMP@R837 can be a potential candidate for preventive cancer vaccines in the clinic.

Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways.

In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed in vitro osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway.

Puerarin inhibits titanium particle-induced osteolysis and RANKL-induced osteoclastogenesis via suppression of the NF-κB signaling pathway.

Osteolysis around the prosthesis and subsequent aseptic loosening are the main causes of prosthesis failure. Inflammation due to wear particles and osteoclast activation are the key factors in osteolysis and are also potential targets for the treatment of osteolysis. However, it is not clear whether puerarin can inhibit chronic inflammation and alleviate osteolysis. In this study, we investigated the effect of puerarin on Ti particle-induced inflammatory osteolysis in vivo in rat femoral models and in vitro in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast activation models. Our in vivo results showed that puerarin significantly inhibited Ti particle-induced osteolysis and the expression of matrix metallopeptidase 9 (MMP-9), nuclear factor of activated T cells 1 (NFATc1), tumour necrosis factor (TNF)-α and interleukin (IL)-6. In vitro, puerarin prevented RANKL-induced osteoclast differentiation, bone resorption and F-actin ring formation in a concentration-dependent manner. Furthermore, puerarin decreased the phosphorylation of p65 and prevented p65 moving from the cytoplasm to the nucleus. Puerarin also reduced the expression of osteoclast-specific factors and inhibited the inflammatory response. In conclusion, our study proves that puerarin can block the NF-κB signalling pathway to inhibit osteoclast activation and inflammatory processes, which provides a new direction for the treatment of osteolysis-related diseases.

Molecular characterization of cotton 14-3-3L gene preferentially expressed during fiber elongation.

The 14-3-3 protein, highly conserved in all eukaryotic cells, is an important regulatory protein. It plays an important role in the growth, amplification, apoptosis, signal transduction, and other crucial life activities of cells. A cDNA encoding a putative 14-3-3 protein was isolated from cotton fiber cDNA library. The cDNA, designated as Gh14-3-3L (Gossypium hirsutum 14-3-3-like), is 1,029 bp in length (including a 762 bp long open reading frame and 5'-/3'-untranslated regions) and deduced a protein with 253 amino acids. The Gh14-3-3L shares higher homology with the known plant 14-3-3 proteins, and possesses the basic structure of 14-3-3 proteins: one dimeric domain, one phosphoralated-serine rich motif, four CC domains, and one EF Hand motif. Northern blotting analysis showed that Gh14-3-3L was predominantly expressed during early fiber development, and reached to the peak of expression in 10 days post anthers (DPA) fiber cells, suggesting that the gene may be involved in regulating fiber elongation. The gene is also expressed at higher level in both ovule and petal, but displays lower or undetectable level of activity in other tissues of cotton.