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Prior research has indicated that bisphosphonates (BPs) can improve periodontal disease because of their anti-osteoporosis properties. In vitro studies have shown that BPs induce cytotoxicity, inhibit wound healing, and thus affect periodontal disease. Denosumab and BPs have alternative indications. BP and denosumab are not known to correlate with gingival disorders. We assessed such a relationship by applying Bayesian and nonproportional analyses to data in the US FDA Adverse Event Reporting System (FAERS) database. The study analyzed BPs and denosumab-reported incidents with preferred terms found in the narrow Standardized MedDRA Queries for gingival disorders. A total of 5863 reported cases of gingival disorders were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, and zoledronate) and denosumab. More than 15% of patients with gingival disorders related to BPs and denosumab other than denosumab were hospitalized over short- or long-term periods. Our findings indicated BPs and denosumab had significant reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) with respect to gingival disorders. Pamidronate had the highest association (ROR = 64.58, PRR = 57.99, IC = 5.71), while the weakest association was found with denosumab (ROR = 3.61, PRR = 3.60, IC = 1.77). Significant associations were found between the six drugs and gingival pain, gingival recession, gingivitis, periodontal disease, and periodontitis. In conclusion, our comprehensive overview of the correlations, clinical characteristics, and prognoses of BPs and denosumab-related gingival disorders suggests that these issues deserve continued surveillance and appropriate management.

Abstract Background Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer. Methods In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis. Results Herein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis. Conclusions Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.

A series of complex 2,2,2-trifluoroethyl fatty acid esters were synthesized by the reaction of fatty acids and phenyl(2,2,2-trifluoroethyl)iodonium triflate in the presence of Cs2CO3. The reaction at room temperature without any other additive provided the corresponding 2,2,2-trifluoroethyl esters in up to quantitative yield. The conjugated carbon–carbon double bonds, the unprotected hydroxyl group, and the amido functionalities in the substrates are all tolerated in the reaction. Compared to the known synthetic methods, advantages of this reaction include mild conditions, good functional group tolerance, and without using harsh and toxic condensation agents, which allows for a green, facile, and efficient way to 2,2,2-trifluoroethyl fatty acid esters.

An amendment to this paper has been published and can be accessed via the original article.

The high-temperature β-phase NaMnO2is a promising material for Na-ion batteries (NIBs) due to its high capacity and abundant resources. However, the synthesis of phase-pure β-NaMnO2is burdensome and costineffective because it needs to be sintered under oxygen atmosphere at high temperature and followed by a quenching procedure. Here we first report that the pure β phase can be stabilized by Cu-doping and easily synthesized by replacing a proportion of Mn with Cu via a simplified process including sintering in air and cooling to room temperature naturally. Based on the first-principle calculations, the band gap decreases from 0.7 eV to 0.3 eV, which indicates that the electronic conductivity can be improved by Cu-doping. The designed β-NaCu0.1 Mn0.9O2is applied as cathode in NIBs, exhibiting an energy density of 419Wh/kg and better performance in terms of rate capability and cycling stability than those in the undoped case. [ABSTRACT FROM AUTHOR]

The effects of technological parameters of solid boroncarburizing and boron-carbon compound carburizing on the microstructure and properties of 12Cr13 martensitic stainless steel were studied.For the co-carburizing，12Cr13 steel was treated by solid borocarburizing heat treatment with different boron-carbon ratios；as for the boron-carbon compound carburizing，12Cr13 martensitic stainless steel was solid carburized first，then the boronizing treatment was carried out to get the optimal composite carburizing parameters.The microhardness，XRD phase structure，corrosion resistance under electrochemistry，friction and wear properties of 12Cr13 martensitic stainless steel samples under the optimum co-carburizing and compound carburizing parameters were tested and analyzed.Results showed that under the co-carburizing conditions of 950 ℃and 6 h，the optimum boron-carbon ratio of borocarburizing agent was 6:4；Under the condition of chemical compound carburizing for 6 h，the optimum parameters of boron-carbon compound carburizing were 950 ℃carburizing and 950 ℃boronizing.After the final heat treatment (quenching＋low temperature tempering) of borocarburizing and compound carburizing test pieces，the hardness of the surface layer could reach 1 507.3 HV0.98 N， and the hardness of the core was 420.6 HV0.98 N.The thickness of the borocarburizing and compound carburizing layers under the optimum parameters was 976 μm and 1 125 μm，respectively.The electrochemical test showed that the corrosion resistance of the material was improved after borocarburizing and boron-carbon compound carburizing，and the corrosion potential was -0.578 V for borocarburizing and -0.582 V for boron-carbon compound carburizing.The wear test showed that the borocarburizing and boron-carbon compound carburizing could significantly improve the wear resistance of 12Cr13 martensitic stainless steel.