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[Display omitted] • Vinyl silica nanoparticles are synthesized and firstly applied to crosslink and enhance preformed particle gels. • State-of-the-art multiple crosslinked preformed particle gels (MC-PPGs) were developed. • MC-PPGs exhibit superior strength with a storage modulus up to 110,000 Pa. • MC-PPGs display exceptional resistance to temperature and salinity as well as broad pH adaptability. • MC-PPGs show ultra-high plugging strength (>14 MPa/m) for open fractures/void space conduit. Preformed particle gels (PPGs) have been identified as an effective method to control conformance and mitigate excessive water production. However, the weak strength of swollen PPGs makes them susceptible to shear failure during formation migration in harsh reservoir conditions. To address this issue, a novel type of multi-crosslinked preformed particle gels (MC-PPGs) with ultra-high strength, exceptional temperature and salinity resistance has been developed. Vinyl silica nanoparticles (VSNPs) were first prepared and used as nano crosslinking agents and enhancing agents in constructing multiple cross-linking structures with macromolecules, functional monomers, and crosslinking agents. MC-PPGs have an elastic modulus up to 110,000 Pa, which is significantly higher than other existing PPGs. Additionally, when exposed to high-salinity environments (e.g., 20 % NaCl and 10 % CaCl 2 + 10 % MgCl 2), MC-PPGs remain for an extended period at elevated temperatures (80 °C for 24 months, 120 °C for 13 months, and over one month at 160 °C). Furthermore, the degradation products of MC-PPGs have minimal impact to reservoir permeability, with a core damage rate below 5 %. MC-PPGs are pH-adaptable (1 < pH < 12), which makes them a promising candidate for reservoirs with supercritical CO 2 flooding. Laboratory coreflooding tests have demonstrated that MC-PPGs provide excellent plugging efficiency (>99.9 %) for fractured cores and ultra-high breakthrough pressure gradients (>14 MPa/m) at varying test temperatures (20 °C, 80 °C, and 120 °C). Considering these unique features, MC-PPGs are ideally suited for oilfield applications. [ABSTRACT FROM AUTHOR]

Background: Activated osteoclasts cause excessive bone resorption, and disrupt bone homeostasis, leading to osteoporosis. The extracellular signal-regulated kinase (ERK) signaling is the classical pathway related to osteoclast differentiation, and mitochondrial reactive oxygen species are closely associated with the differentiation of osteoclasts. Myrislignan (MRL), a natural product derived from nutmeg, has multiple pharmacological activities; however, its therapeutic effect on osteoporosis is unclear. Here, we investigated whether MRL could inhibit osteoclastogenesis and bone mass loss in an ovariectomy mouse model by suppressing mitochondrial function and ERK signaling. Methods: Tartrate-resistant and phosphatase (TRAP) and bone resorption assays were performed to observe the effect of MRL on osteoclastogenesis of bone marrow macrophages. MitoSOX RED and tetramethyl rhodamine methyl ester (TMRM) staining was performed to evaluate the inhibitory effect of MRL on mitochondria. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was performed to detect whether MRL suppressed the expression of osteoclast-specific genes. The impact of MRL on the protein involved in the mitogen-activated protein kinase (MAPK) and nuclear factor-κB pathways was evaluated using western blotting. In addition, a specific ERK agonist LM22B-10, was used to revalidate the inhibitory effect of MRL on ERK. Finally, we established an ovariectomy mouse model to assess the therapeutic effect of MRL on osteoporosis in vivo. Results: MRL inhibited osteoclast differentiation and the associated bone resorption, by significantly decreasing osteoclastic gene expression. Mechanistically, MRL inhibited the phosphorylation of ERK by suppressing the mitochondrial function, thereby downregulating the nuclear factor of activated T cells 1 (NFATc1) signaling. LM22B-10 treatment further verified the targeted inhibition effect of MRL on ERK. Microscopic computed tomographic and histologic analyses of the tibial tissue sections indicated that ovariectomized mice had lower bone mass and higher expression of ERK compared with normal controls. However, MRL treatment significantly reversed these effects, indicating the anti-osteoporosis effect of MRL. Conclusion: We report for the first time that MRL inhibits ERK signaling by suppressing mitochondrial function, thereby ameliorating ovariectomy-induced osteoporosis. Our findings can provide a basis for the development of a novel therapeutic strategy for osteoporosis. [ABSTRACT FROM AUTHOR]

To enhance the surface insulation properties of SiO2/epoxy resin composites, the SiO2 filler is co-modified with a chemical method and dielectric barrier discharge plasma in this work. The effects on the micro-structures, electrical parameters and surface insulation properties of the materials are studied. The results show that chemical modification using the silane coupling agent (KH550) can effectively introduce organo-functional groups into SiO2 filler. On the other hand, plasma modification shows little effect on the organo-functional group but significantly increases the dispersity of the nanoparticles, therefore reducing filler conglobation in epoxy resin composite. The composite samples with SiO2 doping concentration of 1 wt.%, 2 wt.%, 3 wt.%, 5 wt.% and 7 wt.% are prepared and characterized. It is found that the synergy of chemical and plasma methods could significantly improve the surface insulation of composite samples. Through doping 2 wt.% of the co-modified SiO2 filler, the direct current flashover voltage of the composites in dry air at atmospheric pressure can be increased to 1.53 times of the pure epoxy. The enhanced surface insulation properties are explained by the trap effect and the change of electrical parameters through the co-modification process. [ABSTRACT FROM AUTHOR]

Reactive oxidative species (ROS) generation triggers pyroptosis and induces development of inflammatory osteolysis. Hecogenin (HG) has anti-inflammatory and antioxidative property, but its effects on inflammatory osteolysis remains unclear. In our study, we investigated the mechanism of HG on pyroptosis and its effect on inflammatory osteolysis in vitro and in vivo. The impact of HG on osteoclastogenesis was evaluated using cytotoxicity, TRAcP staining and bone resorption assays. The RNA-sequencing was employed to identify potential signaling pathways, and then RT-qPCR, western blot, immunofluorescence, and ELISA were used to verify. To determine the protective effect of HG in vivo , Lipopolysaccharide (LPS)-induced animal models were utilized, along with micro-CT and histological examination. HG suppressed RANKL-induced osteoclast differentiation, bone resorption, NFATc1 activity and downstream factors. RNA-sequencing results showed that HG inhibited osteoclastogenesis by modulating the inflammatory response and macrophage polarization. Furthermore, HG inhibited the NF-κB pathway, and deactivated the NLRP3 inflammasome. HG activated the expression of nuclear factor E2-related factor 2 (Nrf2) to eliminate ROS generation. Importantly, the inhibitory effect of HG on NLRP3 inflammasome could be reversed by treatment with the Nrf2 inhibitor ML385. In viv o, HG prevented the mice against LPS-induced osteolysis by suppressing osteoclastogenesis and inflammatory factors. In conclusion, HG could activate Nrf2 to eliminate ROS generation, inactivate NLRP3 inflammasome and inhibit pyroptosis, thereby suppressing osteoclastogenesis in vitro and alleviating inflammatory osteolysis in vivo, which indicating that HG might be a promising candidate to treat inflammatory osteolysis. [Display omitted] • HG suppressed osteoclast formation and resorption function. • HG modulated the inflammatory response and macrophage polarization. • HG restrained pyroptosis by inactivating NLRP3 inflammasome. • HG suppressed NLRP3 inflammasome involved Nrf2 activation • HG exhibited protective effects against LPS-induced osteolysis in vivo. [ABSTRACT FROM AUTHOR]

[Display omitted] Reactive Oxygen Species (ROS) play an essential role in the pathogenesis of osteoporosis mainly characterized by excessive osteoclasts (OCs) activity. OCs are rich in mitochondria for energy support, which is a major source of total ROS. Tussilagone (TSG), a natural Sesquiterpenes from the flower of Tussilago farfara , has plentiful beneficial pharmacological characteristics with anti-inflammatory and anti-oxidative activity, but its effects and mechanism in osteopathology are still unclear. In our study, we investigated the regulation of ROS generated from the mitochondria in OCs. We found that TSG inhibited OCs differentiation and bone resorption without any cytotoxicity. Mechanistically, TSG reduced RANKL-mediated total ROS level by down-regulating intracellular ROS production and mitochondrial function, leading to the suppression of NFATc1 transcription. We also found that nuclear factor erythroid 2-related factor 2 (Nrf2) could enhance ROS scavenging enzymes in response to RANKL-induced oxidative stress. Furthermore, TSG up-regulated the expression of Nrf2 by inhibiting its proteosomal degradation. Interestingly, Nrf2 deficiency reversed the suppressive effect of TSG on mitochondrial activity and ROS signaling in OCs. Consistent with this finding, TSG attenuated post-ovariectomy (OVX)- and lipopolysaccharide (LPS) induced bone loss by ameliorating osteoclastogenesis. Taken together, TSG has an anti-bone resorptive effect by modulating mitochondrial function and ROS production involved Nrf2 activation. [ABSTRACT FROM AUTHOR]

The plasmonic Au-based bimetallic nanocatalysts have the potential to exhibit superior visible-light (VL) photocatalytic activity, and their performance in reaction is greatly dependent on the method of activation. Herein, Au-Fe/TiO 2 nanocatalysts are prepared by a modified incipient wetness impregnation method with the precursors of HAuCl 4 and FeCl 3. The visible-light activities of the samples activated by calcination at 300 °C, 50%H 2 /Ar plasma and O 2 plasma are compared using CO oxidation. Au-Fe/TiO 2 activated by O 2 plasma has the most exceptional performance with a CO conversion of 90%. The samples are characterized by transmission electron microscopy, UV–vis diffuse reflectance spectroscopy, X-ray photoelectron spectra, and CO chemisorption. It is found that O 2 plasma restructures nano Au and Fe on the TiO 2 support into Au-Fe alloy, preventing nano Au particle size increase. The Au-Fe alloy nanoparticles on TiO 2 has a narrow size distribution and are approximately 4 nm in size. Many surface oxygen species on Au-Fe alloy are observed, as well as a unique board peak assigned to CO adsorption, and they can improve the activity and stability of Au-Fe alloy in CO oxidation. Finally, a reaction mechanism of Au-Fe/TiO 2 activated by O 2 plasma for CO oxidation is developed. This research demonstrates that the treatment of O 2 plasma is an available approach to producing efficient Au-Fe plasmonic nanocatalysts. [Display omitted] • Au-Fe/TiO 2 activated by O 2 plasma has exceptional activity and stability. • O 2 plasma can restructure nano Au and Fe on the TiO 2 support into Au-Fe alloy. • O 2 plasma can prevent the nano Au particle on Au-Fe/TiO 2 to increase. • Many surface oxygen species and a unique board CO adsorption peak were observed. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO) denotes the presence of mature bone tissue in soft tissues or around joints. Inflammation is a key driver of traumatic HO, and macrophages play an important role in this process. Ethyl caffeate (ECF), a critical active compound found in Petunia, exerts significant anti-inflammatory effects. Herein, we established a mouse model of HO by transection of the Achilles tendon and back burn and found abundant macrophage infiltration in the early stage of HO, which decreased with time. In vitro and in vivo experiments indicated that ECF inhibited macrophage polarization, and mechanistic studies showed that it inhibited the SIRT1/NF-κB signalling pathway, thereby suppressing the release of downstream inflammatory cytokines. ECF reduced HO in mice, and its effect was comparable to indomethacin (INDO). In vitro studies revealed that ECF did not directly affect the mineralization of mesenchymal stem cells (MSCs) or osteogenic differentiation but inhibited these processes by reducing the level of inflammatory cytokines in the conditioned medium (CM). Thus, M1 macrophages may play a crucial role in the pathogenesis of HO, and ECF is a prospective candidate for the prevention of trauma-induced HO. Data will be made available on request [Display omitted] • Early stage of heterotopic ossification with infiltration of M1 macrophages. • Ethyl caffeate inhibits macrophage polarization via SIRT1/NF-κB pathway. • Ethyl caffeate inhibits the secretion of inflammatory cytokines in macrophages. • Ethyl caffeate inhibits the formation of heterotopic ossification in mice. [ABSTRACT FROM AUTHOR]

The formation of osteoclasts and their hyperactive bone resorption are related to the aggregation of intracellular reactive oxygen species (ROS). Flavonoids, derived from plant active ingredients, can alleviate the symptoms of osteoporosis (OP). Isosinensetin (Iss) is a flavonoid with antioxidant effects obtained mainly from citrus fruits, and its effect on osteoclastogenesis has not been reported. In this study, we investigated the antioxidant activity of Iss on osteoclast differentiation and function, as well as the therapeutic impact of Iss on OP. We found that Iss inhibited osteoclastogenesis and suppressed the bone resorption function of osteoclasts. Additionally, Iss reduced receptor activator of nuclear factor-κB ligand (RANKL)-induced intracellular ROS. Using quantitative real-time polymerase chain reaction and western blot, we further found that Iss inhibited osteoclast-specific genes and related proteins, while promoting the expression of antioxidant enzyme-related genes and proteins. Mechanistically, Iss reduces intracellular ROS by activating nuclear factor-erythroid 2-related factor 2 (Nrf2) and its related antioxidant enzymes and inhibits the downstream nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways of ROS, which in turn inhibits nuclear factor of activated T cells 1 (NFATc1), and ultimately inhibits osteoclastogenesis. In vivo , by micro-computed tomography (Micro-CT) assay and histological analyses, we found that Iss could reduce bone loss in ovariectomized (OVX) mice. Therefore, Iss has the potential as an OP preventative and therapeutic drug option. [Display omitted] • The formation of osteoblasts requires reactive oxygen species. • A flavonoid with antioxidant properties mainly found in citrus fruits. • Isosinensetin can inhibit osteoclasts by reducing reactive oxygen species. • Isosinensetin can attenuate estrogen deficiency-induced osteoporosis in mice. • Isosinensetin could be a potential drug against osteoporosis. [ABSTRACT FROM AUTHOR]

4-Methylcatechol (4-MC) is an agonist of various neurotrophic factors, which can upregulate the expression of Heme oxygenase 1 (HO-1) protein by activating nuclear factor erythroid 2-related factor 2 (Nrf2), thereby inhibiting oxidative stress-induced neural stem cell death. During RANKL-stimulated osteoclast differentiation, intracellular reactive oxygen species (ROS) levels were increased. Nonetheless, the effect of 4-MC on osteoclast formation and bone resorption function has not been researched. In this study, we investigated the effect of HO-1 upregulation by 4-MC on RANKL-induced osteoclastogenesis and explored the molecular mechanism of HO-1 upregulation by 4-MC. We found that the small molecule compound 4-MC could bind to Keap1 amino acid residue of glycine GLY 367, isoleucine ILE 559 and valine VAL 606, with a predicted binding energy of −4.99 kcal/mol. 4-MC was found to inhibit osteoclast differentiation in vitro by activating Nrf2 to scavenge ROS, inhibiting NF-κB phosphorylation, and alleviating osteoporosis in ovariectomized (OVX) mice. Taken together, 4-MC reduces ROS by inhibiting Keap1, thereby preventing OVX-induced bone loss. • Combination of database chip data and basic experiments. • Methylcatechol (4-MC) attenuates osteoclastogenesis. • 4-MC protects bone mass in mice by regulating ROS/Keap1/Nrf2 signalling axis. • Molecular docking predicted the binding site of 4-MC to protein KEAP1. • 4-MC reduces reactive oxygen species required for osteoclast differentiation. [ABSTRACT FROM AUTHOR]

Bone loss occurs in several inflammatory diseases because of chronic persistent inflammation that activates osteoclasts (OCs) to increase bone resorption. Currently available antiresorptive drugs have severe side effects or contraindications. Herein, we explored the effects and mechanism of Alpinetin (Alp) on receptor activator of nuclear factor κB ligand (RANKL)-mediated OCs differentiation, function, and in inflammatory osteolysis of mice. Primary mouse bone marrow-derived macrophages (BMMs) induced by RANKL and macrophage colony-stimulating factor (M-CSF) were utilized to test the impact of Alp on OCs differentiation, function, and intracellular reactive oxygen species (ROS) production, respectively. Expression of oxidant stress relevant factors and OCs specific genes were assessed via real-time quantitative PCR. Further, oxidative stress-related factors, NF-κB, MAPK, PI3K/AKT/GSK3-β , and NFATc1 pathways were examined via Western blot. Finally, LPS-induced mouse calvarial osteolysis was used to investigate the effect of Alp on inflammatory osteolysis in vivo. Alp suppressed OCs differentiation and resorption function, and down-regulated the ROS production. Alp inhibited IL-1β , TNF-α and osteoclast-specific gene transcription. It also blocked the gene and protein expression of Nox1 and Keap1, but enhanced Nrf2, CAT, and HO-1 protein levels. Additionally, Alp suppressed the phosphorylation of PI3K and P38, and restrained the expression of osteoclast-specific gene Nfatc1 and its auto-amplification, hence minimizing LPS-induced osteolysis in mice. Alp is a novel candidate or therapeutics for the osteoclast-associated inflammatory osteolytic ailment. Alpinetin ameliorates bone loss in LPS-induced inflammation osteolysis of mice via suppressing RANKL-induced osteoclastogenesis through inhibiting inflammation and down-regulating ROS-mediated P38/PI3K signaling pathway. [Display omitted] • Bone loss occurs in various inflammatory diseases, and osteoclasts are the only bone resorbing cells. • Alpinetin inhibits inflammation and intracellular ROS generation in osteoclastogenesis. • Alpinetin suppresses osteoclasts differentiation and function via down-regulating P38 and PI3K-NFATc1 signaling axis. • Alpinetin plays a therapeutic effect on inflammatory osteolysis in mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • EMCL suppresses RANKL-induced osteoclastogenesis and resorption function. • EMCL could bind to the active pocket of the structural domains of ERK1 and ERK2 kinases. • EMCL inhibits RANKL-induced activation of the ERK/MAPK pathway. • EMCL can resist osteoporosis caused by estrogen deficiency. The hyperactivity of osteoclasts caused by postmenopausal estrogen deficiency plays an imperative role in the progression of osteoporosis. Although osteoporosis-related drugs have been widely used to alleviate this disorder, there is an urgent need for drugs with fewer side effects. In this study, we found that epoxymicheliolide (EMCL), a derivative of parthenolide, has a high affinity to ERK1/2, but the treatment and mechanism of osteoporosis using EMCL have not been explored. Therefore, we intended to figure out the effects and potential mechanisms of EMCL on RANKL-stimulated osteoclast formation and function in vitro , construct an OVX murine model to simulate the therapeutic effects of EMCL on estrogen-deficient bone loss subsequently. EMCL restrained the phosphorylation of ERK1/2 in the RANKL-stimulated MAPK pathway, which in sequence inhibited the transcription and expression of the main osteoclast transcription factor NFATc1, resulting in the suppression of osteoclastogenesis and bone resorption. However, the same concentration of EMCL did not affect the proliferation and differentiation of osteoblasts. In vivo experiments showed that EMCL can significantly resist osteoporosis caused by estrogen deficiency, alleviate bone loss, and reduce the number of osteoclasts. These results suggest that EMCL can reduce osteoclast production and bone resorption by inhibiting ERK1/2 phosphorylation and NFATc1 entering the nucleus, and could be used in the treatment of osteoporosis caused by estrogen deficiency and hyperactivity of osteoclasts. [ABSTRACT FROM AUTHOR]

[Display omitted] Excessive bone erosion by osteoclasts is associated with osteoporosis, rheumatoid arthritis, and periprosthetic osteolysis. Targeting osteoclasts may serve as an effective treatment for osteolytic diseases. Although drugs are currently available for the treatment of these diseases, exploring potential anti-osteoclast natural compounds with safe and effective treatment remains needed. Oroxylin A (OA), a natural flavonoid isolated from the root of Scutellaria baicalensis Georgi , has numerous beneficial pharmacological characteristics, including anti-inflammatory and antioxidant activity. However, its effects and mechanisms on osteoclast formation and bone resorption have not yet been clarified. Our research showed that OA attenuated the formation and function of osteoclast induced by RANKL in a time- and concentration-dependent manner without any cytotoxicity. Mechanistically, OA suppressed intracellular reactive oxygen species (ROS) levels through the Nrf2-mediated antioxidant response. Moreover, OA inhibited the activity of NFATc1, the master transcriptional regulator of RANKL-induced osteoclastogenesis. OA exhibited protective effects in mouse models of post-ovariectomy (OVX)- and lipopolysaccharide (LPS)‐induced bone loss, in accordance with its in vitro anti-osteoclastogenic effect. Collectively, our findings highlight the potential of OA as a pharmacological agent for the prevention of osteoclast-mediated osteolytic diseases. [ABSTRACT FROM AUTHOR]