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Objective: Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss. Methods: To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed in vitro. Results: CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68+ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163. Conclusion: Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.

Abstract The Structure Building Framework has suggested that inhibitory control plays an important role in metaphor comprehension, yet it remains less clear how the role varies with different types of L2 metaphors in the absence or presence of context. We used a modified flanker task to measure the inhibitory control ability of Chinese-English bilinguals who were divided into two groups: high inhibitory control (HIC) and low inhibitory control (LIC). They performed semantic judgment tasks in which L2 conventional and novel metaphors were presented in isolated sentences (Experiment 1), and the same metaphors were preceded by supportive or literal contexts (Experiment 2). In Experiment 1, the HIC group responded significantly slower than the LIC group to novel metaphors, with no obvious distinction between the groups for conventional metaphors. In Experiment 2, the HIC group performed significantly faster on novel metaphors in supportive contexts than in literal contexts, while the LIC group had no such facilitative effect. However, the LIC group’s response to conventional metaphors was greatly facilitated by supportive contexts, whereas the HIC group showed no significant difference in two context conditions. These results suggest that inhibitory control is selectively recruited in the comprehension of L2 conventional and novel metaphors under different contextual demands. This finding provides a comprehensive account of the flexible role of inhibitory control in L2 metaphor comprehension.

Abstract The assembly of polymers at liquid-liquid interfaces offers a promising strategy for fabricating two-dimensional polymer films. However, a significant challenge arises when the polymers lack inherent interfacial traction. In response, we introduce an approach termed chaperone solvent-assisted assembly. This approach utilizes a target polymer, X, along with three solvents: α, β, and γ. α and β are poor solvents for X and immiscible with each other, while γ is a good solvent for X and miscible with both α and β, thus serving as the chaperone solvent. The cross-interface diffusion of γ induces the assembly of interfacially nonactive X at the α-β interface, and this mechanism is verified through systematic in situ and ex situ studies. We show that chaperone solvent-assisted assembly is versatile and reliable for the interfacial assembly of polymers, including those that are interfacially nonactive. Several practical applications based on chaperone solvent-assisted assembly are also demonstrated.

In this article, we use the method of sample analysis to analyze the current development of China's financial industry and the impact of the financial industry on the current economy. In the process of analysis, we found that China's economic development is unbalanced. The eastern part has a fast development process, while the western part has a slow development process, and the economic independence is poor. Export-oriented income accounts for a large proportion of total income. The original data system has defects and cannot provide a reliable source of data for the embedded database. Therefore, we have developed an analysis system that can be applied to the embedded database to more accurately predict the impact of the financial industry on economic development. The alternative model used later gave dynamic analysis capabilities that the original analysis system did not possess, and improved the predictability of the financial environment by enhancing the variability of the system, thus achieving breakthrough achievements in analysis. Through various research investigations, we can find that embedded databases have their unique advantages in many aspects. At present, due to the development of the multimedia industry, the pace of joint development of intelligent AI technology and the financial industry is also accelerating, which brings more development opportunities while also bringing many challenges. Therefore, the traditional financial industry needs to undergo transformation. The advancement of science and technology is the fundamental driving force for the development of every industry. Therefore, we need to increase investment in science and technology, cultivate new talents, enhance risk control capabilities, strengthen supervision of the industry, and enhance the intelligent level of industry development.

Objectives: During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage. Methods: This study was a follow-up trial of the “Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial.” Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines. Results: The geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period. Conclusion: Co-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.

Abstract Piezoelectric biomaterials have attracted great attention owing to the recent recognition of the impact of piezoelectricity on biological systems and their potential applications in implantable sensors, actuators, and energy harvesters. However, their practical use is hindered by the weak piezoelectric effect caused by the random polarization of biomaterials and the challenges of large-scale alignment of domains. Here, we present an active self-assembly strategy to tailor piezoelectric biomaterial thin films. The nanoconfinement-induced homogeneous nucleation overcomes the interfacial dependency and allows the electric field applied in-situ to align crystal grains across the entire film. The β-glycine films exhibit an enhanced piezoelectric strain coefficient of 11.2 pm V−1 and an exceptional piezoelectric voltage coefficient of 252 × 10−3 Vm N−1. Of particular significance is that the nanoconfinement effect greatly improves the thermostability before melting (192 °C). This finding offers a generally applicable strategy for constructing high-performance large-sized piezoelectric bio-organic materials for biological and medical microdevices.

The free radical trapping capacities of multiple pyranoanthocyanins in wine storage and ageing were theoretically explored by density functional theory (DFT) methods. Intramolecular hydrogen bonds were detected in all pyranoanthocyanins, and the planarity of the compounds worsened with an increasing dielectric constant in the environment. Solvents significantly influenced the reaction enthalpies; thus, the preferred thermodynamic mechanisms of the free radical scavenging reactions were modified in different phases. This study incorporates hydrogen atom transfer (HAT), proton loss (PL), electron transfer (ET) reactions, and demethylation (De) of methoxy group mechanisms. The three pyranoanthocyanins have the capacity to capture n1+1 free radicals, where n1 represents the number of methoxy groups. In the gas phase, they prefer employing the n1-De-HAT mechanism on the guaiacyl moiety of the B ring, resulting in the formation of a stable quinone or a quinone radical to scavenge free radicals. In the benzene phase, pyranoanthocyanins trap free radicals via a PL−n1−De−HAT mechanism. In the water phase, the targeted pyranoanthocyanins may dissociate in the form of carboxylate and tend to utilize the n2−PL−n1−De−ET mechanism, where n2 and n1 represent the number of phenolic groups and methoxy groups, respectively, facilitating multiple H+/e− reactions.

It is important to have a deep understanding of microbial diversity–multifunctionality relationships. Studies on α diversity of microorganisms have been reported extensively, but the different microbial species of diversity at β scale is still unclear. In this study, we selected bare patches (BP), vegetated patches (VP) and healthy alpine meadows (AM) of different degradation severity in different restoration succession stages to investigate the microbial α and β diversity (bacteria and fungi), and soil multifunctionality (i.e. plant aboveground biomass, belowground biomass, soil organic carbon, total nitrogen, total phosphorus, ammonium nitrogen, nitrate nitrogen, and available phosphorus) to analyze the relationship between each other. The results show that the most crucial limiting factors were soil pH and moisture in the natural restoration succession stages of degraded patches, and soil moisture affects pH and mediates the microbial diversity–multifunctionality relationships. Fungal β diversity and multifunctionality were positively correlated, bacterial α diversity and multifunctionality were negatively correlated. Soil pH not only directly impacts on multifunctionality, but also indirectly affects multifunctionality by influencing bacterial α and fungal β diversity. These results indicate that fungal β diversity can positively predict soil multifunctionality, and is the key mediator of soil pH and multi-functionality. Our findings highlight the potential of fungal β diversity to improve soil multifunctionality in the natural restoration succession stages of degraded meadow patches.

Objective: There is very limited evidence in the NHANES database linking serum apolipoprotein B and lumbar bone mineral density (BMD) in adults aged 20–59 years. There are few studies associating apolipoprotein B concentrations with BMD, and there is some debate about the association between obesity and BMD. Therefore, the purpose of this study was to determine the association between serum apolipoprotein B concentrations and lumbar spine BMD in adults aged 20–59 years and to predict its association with risk of osteopenia or osteoporosis.Methods: A cross-sectional study of the entire US ambulatory population was conducted using data from the National Health and Nutrition Examination Survey (NHANES) database. Weighted multiple regression equation models were used to assess the association between serum apolipoprotein B and lumbar BMD. A logistic weighted regression model was used to assess the association between serum apolipoprotein B concentrations and risk of osteopenia or osteoporosis. Subsequent stratified analyses were performed to refine the primary population of association.Results: Our study showed a significant negative association between serum apolipoprotein B concentration and lumbar BMD and a significant positive association with the risk of osteoporosis or osteopenia in the total population. After stratifying by sex, age and race, we concluded differently. The association of serum apolipoprotein B concentration with lumbar spine BMD and risk of osteopenia or osteoporosis was significant in male, but not in female. After stratification by age, the negative association between serum apolipoprotein B concentrations and lumbar BMD and the positive association with risk of osteopenia or osteoporosis was more significant in the 30–39 and 50–59 years age groups. When stratified by race, serum apolipoprotein B concentrations were significantly negatively associated with lumbar BMD and positively associated with risk of osteopenia or osteoporosis in Mexican American and non-Hispanic black populations. Thus, these findings suggest that these associations are influenced by sex, age, and race, respectively.Conclusion: Our results suggest that the association between serum apolipoprotein B levels and the risk of lumbar BMD and osteopenia or osteoporosis varies by sex, age, and race. In men, elevated serum apolipoprotein B levels were negative for bone quality. Elevated serum apolipoprotein B levels in the age groups 30–39 and 50–59 years also had a negative effect on bone quality. In the Mexican American and Non-Hispanic Black populations, elevated serum apolipoprotein B levels also had a significant negative effect on bone quality.

Natural flavonoids are renowned for their exceptional antioxidant properties, but their limited water solubility hampers their bioavailability. One approach to enhancing their water solubility and antioxidant activity involves the use of cyclodextrin (CD) inclusion. This study investigated the impact of CD inclusion on the three primary radical scavenging mechanisms associated with flavonoid antioxidant activity, utilizing apigenin as a representative flavonoid and employing density functional theory (DFT) calculations. Initially, the optimized geometries of CD−apigenin inclusion complexes were analyzed, revealing the formation of hydrogen bonds between CD and apigenin. In less polar environments, the inclusion complex strengthened the bond dissociation enthalpies of hydroxyl groups, thereby reducing antioxidant activity. Conversely, in polar environments, the inclusion complex had the opposite effect by lowering proton affinity. These findings align with experimental results demonstrating that CD inclusion complexation enhances flavonoid antioxidant activity in aqueous ethanol solutions.

In this study, we analyzed the C, N, and P contents and stoichiometric characteristics of forage leaves of five species (Elymus breviaristatus cv. Tongde, Poa crymophila cv. Qinghai, Puccinellia tenuiflora cv. Qinghai, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai) in “fertilizer-reconstructed soil” through integrative soil amendment with parched sheep manure and granular organic fertilizer in an alpine mining area. A model is fitted in order to screen out the best forage species suitable for vegetation restoration in the alpine mining area and the most favorable fertilizer dosage to improve the nutrient content of forage leaves. The results showed that (1) increasing the dosages of granular organic fertilizer and sheep manure had little effect on the C content of the five types of forage grasses, but they could significantly increase the N and P contents and N/P of the manually restored grassland in the alpine mining area (p < 0.05). (2) The productivity and stability of the five species were ranked as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa pratensis cv. Qinghai > Poa crymophila cv. Qinghai. (3) According to the fitted least squares model and the willingness to maximize the C, N, and P contents of the leaves, the ranking of the five forage grasses was described by the Prediction Profiler as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa crymophila cv. Qinghai > Poa pratensis cv. Qinghai. (4) The predictive model suggested that the optimal contents of C, N, and P in Elymus breviaristatus cv. Tongde, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai leaves could be achieved with the application of 3.6 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. For Poa crymophila cv. Qinghai leaves, the ideal content was attained by applying 0 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. Lastly, the optimal C, N, and P contents in Puccinellia tenuiflora cv. Qinghai leaves could be obtained through the application of 3.6 kg/m2 of granular organic fertilizer combined with 0 kg/m2 of sheep manure. In conclusion, the study’s results highlight the significant practical value of the fertilizer-reconstructed soil for vegetation restoration in alpine mining regions.

Severe degradation of alpine meadow in the Source Zone of the Yellow River (SZYR) seriously affects the stability and sustainability of the local grassland ecosystem. Although some progress has been made in understanding the degradation process, mechanism and restoration, existing restoration technologies do not target at topographic and hydrothermal conditions, resulting in instability and poor sustainability of the restored ecosystem. This study quantified the effects of grassland degradation severity (non-degraded patch (NP), vegetated patch (VP), bare patch (BP)) on the soil physical, chemical properties and microbial community composition and their interactions in the alpine meadow in the SZYR on the Eastern Qinghai-Tibet Plateau, West China. Results showed that as the degradation severity worsens from NP to BP, soil moisture, total porosity, electrical conductivity, and root biomass decreased significantly, while soil bulk density and permeability increased significantly. The contents of soil organic carbon, total nitrogen and total phosphorus decreased significantly with the enlargement of meadow patches. There were significant differences in community structure and functional microorganisms of soil bacteria and fungi in different meadow patches. In conclusion, strategies such as replanting local grass species, adding organic fertilizer and microbial fertilizers and increasing soil compaction intensity of patches to maintain soil moisture, should be considered for restoring the degraded meadow patches.

BackgroundRubella is a highly contagious viral infection with mild manifestations that occurs most often in children and young adults. Infection during pregnancy, especially during the first trimester, can result in an infant born with congenital rubella syndrome (CRS). The purpose of this paper is to analyze the characteristics of rubella epidemics in Anhui province from 2012 to 2021 and explore the prevention and control strategies of rubella.MethodsA descriptive epidemiological approach was used to examine the epidemiological characteristics of rubella in Anhui Province between 2012 and 2021.ResultsFrom 2012 to 2021, a total of 4,987 cases of rubella were reported in Anhui province, with an average annual incidence of 8.11 per million, demonstrating an overall downward trend (χ2 trend =3141.06, P < 0.01). The average yearly incidence of rubella in southern Anhui, central Anhui, and northern Anhui were 9.99 per million, 11.47 per million, and 4.50 per million, respectively, with statistically significant differences (χ2 =792.50, P < 0.01). The male to female incidence ratio was 1.67:1, and the male incidence rate was higher than the female incidence rate. Most cases occurred among students, accounting for 56.59% of all cases, and the 10–34 age group accounted for ~73.71% of all cases. Regarding immunization history, 3.57% of cases had two doses or more, 6.62% had one dose, 16.40% had none, and the remainder were uncertain.ConclusionThe incidence of rubella in Anhui province from 2012 to 2021 continued to decline, with regional variations observed. The 10–34-year-old population without a history of rubella vaccination is at high risk for the disease. It is suggested to carry out rubella vaccination and congenital rubella syndrome monitoring according to the actual situation.

Humans can understand thousands of abstract words, even when they do not have clearly perceivable referents. Recent views highlight an important role of social experience in grounding of abstract concepts and sub-kinds of abstract concepts, but empirical work in this area is still in its early stages. In the present study, a picture-word semantic priming paradigm was employed to investigate the contribution effect of social experience that is provided by real-life pictures to social abstract (SA, e.g., friendship, betrayal) concepts and emotional abstract (EA, e.g., happiness, anger) concepts. Using a lexical decision task, we examined responses to picture-SA word pairs (Experiment 1) and picture-EA word pairs (Experiment 2) in social/emotional semantically related and unrelated conditions. All pairs shared either positive or negative valence. The results showed quicker responses to positive SA and EA words that were preceded by related vs. unrelated prime pictures. Specifically, positive SA words were facilitated by the corresponding social scene pictures, whereas positive EA words were facilitated by pictures depict the corresponding facial expressions and gestures. However, such facilitatory effect was not observed in negative picture-SA/EA word conditions. This pattern of results suggests that a facilitatory effect of social experience on abstract concepts varies with different sub-kinds of abstract concepts, that seems to be limited to positive SA concepts. Overall, our findings confirm the crucial role of social experience for abstract concepts and further suggest that not all abstract concepts can benefit from social experience, at least in the semantic priming.

Objective: The antibacterial activity of copper (Cu)-alloy biomaterials has shown a great potential in clinical application. Here, we evaluated the osteogenesis and antibacterial effects of Ti6Al4V-6.5wt%Cu alloy in an in vivo model of infected bone defects and determine their responsible proteins and pathways using proteomics. Methods: After bone defects were filled with Ti6Al4V and Ti6Al4V-6.5wt%Cu implants for 6 week, the tissue and bone samples around the implants were harvested for radiographic, micro-CT, histological, and bone-related gene expression analyses. An iTRAQ-based protein identification/quantification approach was used to analyze the osteogenic and antibacterial effects of Ti6Al4V-6.5wt%Cu alloy. Results: Imaging and histological results showed Ti6Al4V alloy induced a stronger inflammatory response than Ti6Al4V-6.5wt%Cu alloy; imaging results and osteogenic protein levels showed Ti6Al4V-6.5wt%Cu alloy exerted a stronger osteogenic effect. In vitro experiment, we found the Ti6Al4V-6.5wt%Cu had significant antibacterial effects and inhibited the activity of Staphylococcus aureus in the early stage. In addition, the bacterial biofilm formed in Ti6Al4V-6.5wt%Cu group was significantly lower than that in Ti6Al4V group. Proteomic screening of 4279 proteins resulted in 35 differentially expressed proteins for further examination which were mainly associated with the cellular process, metabolic process, stimulus response, and cellular component organization. In further exploration of the mechanism of osteogenic mineralization of Ti6Al4V-6.5wt%Cu alloy, we found out SDC4 and AGRN were the top two target proteins associated with osteogenic differentiation and bone mineralization. Conclusion: Ti6Al4V-6.5wt%Cu alloy shows a great potential as a bone implant material due to its positive effects against bacterial infection and on bone formation. The Translational potential of this article: At present, titanium alloys and other non-antibacterial metal materials are used in orthopedic internal fixation operations. Our study demonstrates that Ti6Al4V-6.5wt%Cu alloy has good antibacterial and osteogenic effects in vivo and in vitro. This means that Ti6Al4V-6.5wt%Cu alloy may become a new kind of antimicrobial metallic material as internal fixation material to continuously exert its antimicrobial effects and reduce the infection rate after clinical internal fixation.

Glucocorticoids (GCs) inhibit bone angiogenesis and affect bone development, but the underlying mechanisms remain unclear. Here, the authors show that GCs induce vascular cell senescence during bone development by inhibiting angiogenin secretion from osteoclasts, impairing angiogenesis via endothelial Plexin B2, resulting in unpaired bone growth.

Senolytics are a class of drugs that selectively eliminate senescent cells and ameliorate senescence-associated disease. Studies have demonstrated the accumulation of senescent disc cells and the production of senescence-associated secretory phenotype decrease the number of functional cells in degenerative tissue. It has been determined that clearance of senescent cell by senolytics rejuvenates various cell types in several human organs, including the largest avascular structure, intervertebral disc (IVD). The microvasculature in the marrow space of bony endplate (BEP) are the structural foundation of nutrient exchange in the IVD, but to date, the anti-senescence effects of senolytics on senescent vascular endothelial cells in the endplate subchondral vasculature remains unclear. In this study, the relationships between endothelial cellular senescence in the marrow space of the BEP and IVD degeneration were investigated using the aged mice model. Immunofluorescence staining was used to evaluate the protein expression of P16, P21, and EMCN in vascular endothelial cells. Senescence-associated β-galactosidase staining was used to investigate the senescence of vascular endothelial cells. Meanwhile, the effects of senolytics on cellular senescence of human umbilical vein endothelial cells were investigated using a cell culture model. Preliminary results showed that senolytics alleviate endothelial cellular senescence in the marrow space of BEP as evidenced by reduced senescence-associated secretory phenotype. In the aged mice model, we found decreased height of IVD accompanied by vertebral bone mass loss and obvious changes to the endplate subchondral vasculature, which may lead to the decrease in nutrition transport into IVD. These findings may provide evidence that senolytics can eliminate the senescent cells and facilitate microvascular formation in the marrow space of the BEP. Targeting senescent cellular clearance mechanism to increase nutrient supply to the avascular disc suggests a potential treatment value of senolytics for IVD degenerative diseases.

Summary: Background: Abnormal bone formation in subchondral bone resulting from uncoupled bone remodeling is considered a central feature in osteoarthritis (OA) pathogenesis. H-type vessels can couple angiogenesis and osteogenesis. We previously revealed that elevated H-type vessels in subchondral bone were correlated with OA and focal adhesion kinase (FAK) in MSCs is critical for H-type vessel formation in osteoporosis. The aim of this study was to explore the correlation between H-type vessels and MSCs in OA pathogenesis through regulation of H-type vessel formation using defactinib (an FAK inhibitor). Methods: In vivo: 3-month-old male C57BL/6J (WT) mice were randomly divided into three groups: sham controls, vehicle-treated ACLT mice, and defactinib-treated ACLT mice (25 mg/kg, intraperitoneally weekly). In vitro: we explored the role of conditioned medium (CM) of MSCs from subchondral bone of different groups on the angiogenesis of endothelial cells (ECs). Flow cytometry, Western blotting, ELISA, real time (RT)-PCR, immunostaining, CT-based microangiography, and bone micro-CT (μCT) were used to detect changes in relative cells and tissues. Results: This study demonstrated that inhibition of H-type vessels with defactinib alleviated OA by inhibiting H-type vessel-linked MSCs in subchondral bone. During OA pathogenesis, H-type vessels and MSCs formed a positive feedback loop contributing to abnormal bone formation in subchondral bone. Elevated H-type vessels provided indispensable MSCs for abnormal bone formation in subchondral bone. Flow cytometry and immunostaining results confirmed that the amount of MSCs in subchondral bone was obviously higher in vehicle-treated ACLT mice than that in sham controls and defactinib-treated ACLT mice. In vitro, p-FAK in MSCs from subchondral bone of vehicle-treated ALCT mice increased significantly relative to other groups. Further, the CM from MSCs of vehicle-treated ACLT mice enhanced angiogenesis of ECs through FAK-Grb2-MAPK-linked VEGF expression. Conclusions: Our results demonstrate that defactinib inhibits OA by suppressing the positive feedback loop between H-type vessels and MSCs in subchondral bone. The translational potential of this article: Our results provide a mechanistic rationale for the use of defactinib as an effective candidate for OA treatment.

Abstract Background Prenatal dexamethasone exposure (PDE) induces low birth weight and retardation of fetal bone development which are associated with lower peak bone mass in adult offspring. Here we evaluated whether and how PDE affects postnatal long bone growth in mouse offspring. Methods Pregnant mice were injected subcutaneously with dexamethasone (1.2 mg/kg/day) every morning from gestational days (GD) 12–14. Femurs and tibias of 2-, 4-, 6-, and 12-week-old female offspring were harvested for histological, immunofluorescence, flow cytometric analysis, or microcomputed tomography (μCT) measurement. Results PDE leads to impaired bone remodeling as well as decreased bone mass in the long bone of female mouse offspring. During postnatal bone growth, significant decrease of CD45−CD29+CD105+Sca-1+ bone marrow mesenchymal stem cells (BMSCs) and CD45−Nestin+ cells, loss of type H vessels, and increment of cellular senescence were found in metaphysis of long bone in mouse offspring after PDE. We further show that eliminating the excessive senescent cells with dasatinib (5 mg/kg/day) and quercetin (50 mg/kg/day) during GD 12–14 rescues the above toxic effect of PDE on the postnatal long bone growth in female mouse offspring. Conclusion Cellular senescence mediates the toxic effect of PDE on postnatal long bone growth in mouse offspring, and inhibition of cellular senescence may be proposed for treating the retardation of bone growth caused by PDE.

Background: As an effective antitumor drug, doxorubicin (DOX) is primarily used to treat solid tumors and hematologic malignancies. However, increasing evidence has emerged indicating its cardiotoxicity, and few solutions have been proposed to counter this side effect. Higenamine (HG) is a natural compound widely found in many Chinese herbs and also serves as a component in many healthcare products. Several studies have demonstrated its cardioprotective effect in different models, but little is known about the underlying influences of HG against myocardial damage from DOX-induced chronic cardiotoxicity.Methods and Results: C57BL/6 mice and neonatal rat ventricular cardiomyocytes (NRVMs) were used to evaluate the cardioprotective effect of HG against DOX-induced myocardial damage. In mice, DOX (intraperitoneally injected 5 mg/kg every 3 days for 4 weeks) significantly increased cardiomyocyte apoptosis, cardiac atrophy, and cardiac dysfunction, which were significantly attenuated by HG (intragastrically administered with 10 mg/kg every day for 4 weeks). In NRVMs, DOX (3 μM for 24 h) significantly increased cell apoptosis and the level of reactive oxygen species while reducing the level of superoxide dismutase and mitochondrial membrane potential. Remarkably, HG can reverse these pathological changes caused by DOX. Interestingly, the protective effect of HG on DOX-induced cardiotoxicity was independent of the activation of the beta-2 adrenergic receptor (β2-AR), known for mediating the effect of HG on antagonizing ischemia/reperfusion-induced cardiac apoptosis. Furthermore, HG attenuated the abnormal activation of phosphorylated adenosine-activated protein kinase (AMPK). Consistently, AMPK agonists (AICAR) can eliminate these pharmacological actions of HG.Conclusion: Collectively, our results suggested that HG alleviated DOX-induced chronic myocardial injury by suppressing AMPK activation and ROS production.

As the population of most nations have a large proportion of older individuals, there is an increase in the prevalence of osteoporosis. Consequently, scientists have focused their attention on the pathogenic mechanisms of osteoporosis. Owing to an increase in studies on cellular senescence in recent years, research has begun to focus on the function of the senescent microenvironment in osteoporosis. With chronic inflammation, senescent cells in the bone marrow secrete a series of factors known as senescence-associated secretory phenotype (SASP) factors, acting on their own or surrounding healthy cells and consequently exacerbating ageing.The components of the SASP may differ depending on the cause of osteoporosis. This review aimed to summarize the relationship between SASP factors and osteoporosis and suggest new insights into the mechanistic investigation of osteoporosis.

Current research suggests that chronic high-fat dietary intake can lead to bone loss in adults; however, the mechanism by which high-fat diets affect the development of osteoporosis in individuals is unclear. As high-fat diets are strongly associated with ferroptosis, whether ferroptosis mediates high-fat diet-induced bone loss was the focus of our current study. By dividing the mice into a high-fat diet group, a high-fat diet + ferroptosis inhibitor group and a normal chow group, mice in the high-fat group were given a high-fat diet for 12 weeks. The mice in the high-fat diet + ferroptosis inhibitor group were given 1 mg/kg Fer-1 per day intraperitoneally at the start of the high-fat diet. Microscopic CT scans, histological tests, and biochemical indicators of ferroptosis were performed on bone tissue from all three groups at the end of the modelling period. Mc3t3-E1 cells were also used in vitro and divided into three groups: high-fat medium group, high-fat medium+ferroptosis inhibitor group, and control group. After 24 hours of incubation in high-fat medium, Mc3t3-E1 cells were assayed for ferroptosis marker proteins and biochemical parameters, and osteogenesis induction was performed simultaneously. Cellular alkaline phosphatase content and expression of osteogenesis-related proteins were measured at day 7 of osteogenesis induction. The results showed that a high-fat diet led to the development of femoral bone loss in mice and that this process could be inhibited by ferroptosis inhibitors. The high-fat diet mainly affected the number of osteoblasts produced in the bone marrow cavity. The high-fat environment in vitro inhibited osteoblast proliferation and osteogenic differentiation, and significant changes in ferroptosis-related biochemical parameters were observed. These findings have implications for the future clinical treatment of bone loss caused by high-fat diets.

Non-equilibrium systems of immiscible liquids have significant potential to advance different technologies, but control over morphology or functionality remains unexplored. Here, the authors demonstrate an all-liquid fluidic device by exploiting surfactant assemblies to produce a semi-permeable membrane between the liquids.

In the mammalian skeletal system, osteogenesis and angiogenesis are closely linked by type H vessels during bone regeneration and repair. Our previous studies confirmed the promotion of these processes by copper-containing metal (CCM) in vitro and in vivo. However, whether and how the coupling of angiogenesis and osteogenesis participates in the promotion of bone regeneration by CCM in vivo is unknown. In this study, M2a macrophages but not M2c macrophages were shown to be immunoregulated by CCM. A CCM, 316L−5Cu, was applied to drilling hole injuries of the tibia of C57/6 mice for comparison. We observed advanced formation of cortical bone and type H vessels beneath the new bone in the 316L−5Cu group 14 and 21 days postinjury. Moreover, the recruitment of CD206-positive M2a macrophages, which are regarded as the primary source of platelet-derived growth factor type BB (PDGF-BB), was significantly promoted at the injury site at days 14 and 21. Under the stimulation of CCM, mitochondria-derived reactive oxygen species were also found to be upregulated in CD206hi M2a macrophages in vitro, and this upregulation was correlated with the expression of PDGF-BB. In conclusion, our results indicate that CCM promotes the evolution of callus through the generation of type H vessels during the process of bone repair by upregulating the expression of PDGF-BB derived from M2a macrophages.

Antenatal corticosteroid therapy (ACT) has been shown to reduce morbidity and mortality rates in preterm delivery, but the fetus is more likely to face the risk of low bone mineralization and low fetal linear growth. However, the mechanism of ACT inducing low bone mineralization remains largely unknown. Pre-osteoclasts, which play an important role in angiogenesis and osteogenesis, are specifically regulating type H vessels (CD31hiEmcnhi) and vessel formation by secreting platelet-derived growth factor-BB (PDGF-BB). We find that the number of pre-osteoclasts and POC-secreted PDGF-BB is dramatically decreased in ACT mice, contributing to the reduction in type H vessels and bone mineralization during the mouse offspring. Quantitative analyses of micro-computed tomography show that the ACT mice have a significant reduction in the mass of trabecular bone relative to the control group. Mononuclear pre-osteoclasts in trabecular bone decreased in ACT mice, which leads to the amount of PDGF-BB reduced and attenuates type H vessel formation. After sorting the Rank+ osteoclast precursors using flow cytometry, we show that the enhancer of zeste homolog 2 (Ezh2) expression is decreased in Rank+ osteoclast precursors in ACT mice. Consistent with the flow data, by using small molecule Ezh2 inhibitor GSK126, we prove that Ezh2 is required for osteoclast differentiation. Downregulating the expression of Ezh2 in osteoclast precursors would reduce PDGF-BB production. Conditioned medium from osteoclast precursor cultures treated with GSK126 inhibited endothelial tube formation, whereas conditioned medium from vehicle group stimulated endothelial tube formation. These results indicate Ezh2 expression of osteoclast precursors is suppressed after ACT, which reduced the pre-osteoclast number and PDGF-BB secretion, thus inhibiting type H vessel formation and ACT-associated low bone mineralization.

Bone is innervated, and its turnover is affected by sympathetic nerve activity. Here, the authors show that prostaglandin E2, secreted by osteoblasts, activates the EP4 receptor on sensory nerves, inhibiting sympathetic nerve activity and modulating bone formation in mice.

Mesenchymal stem cells are essential for bone development, but it is unclear if their activity is maintained after late puberty, when bone growth decelerates. The authors show that during late puberty in mice, these cells undergo senescence under the epigenetic control of Ezh2.

It is unclear what regulates the fate of mesenchymal stem cells (MSCs) in arterial repair following injury. Here, the authors show that MSC differentiation following injury is triggered by RhoA which in turn stimulates the release of connective tissue growth factor and vascular endothelial growth factor.

The sedimentary facies, diagenetic facies and fracture facies of the Upper Triassic Yanchang Formation Member 8 (Chang 8) reservoir in the Jiyuan region were studied using core observation, thin section, logging and drilling data. On this basis, the petrophysical faices of Chang 8 oil layers were examined to evaluate the pore structure by classification and predict zones with high porosity and permeability. The petrophysical facies were divided according to the superposition and combination of sedimentary facies, diagenetic facies and fracture facies. A number of petrophysical facies of Chang 8 oil layers such as underwater distributary channel, dissolution of unstable components, high-angle fracture, were identified in this way. Four main categories of petrophysical facies were summed up according to the constructive and destructive impact of sedimentary facies, diagenetic facies and fracture facies on the reservoir property and pore structure. Since the reservoir quality index (RQI) is an optimal indicator for describing the reservoir micro-pore structure quantitatively, the value of RQI of different petrophysical facies was calculated respectively. So the classification and evaluation of Chang 8 reservoir pore structure in a single well were realized by the division of petrophysical facies combined with logging data. At last, the vertical and horizontal distribution of sedimentary micro-facies and diagenetic facies of each single layer of Chang 8 oil layers were mapped, the distribution of favorable petrophysical facies can be used to predict the zones with high porosity and permeability. Key words: petrophysical facies, sedimentary facies, diagenetic facies, fracture facies, pore structure, classification and evaluation, Ordos basin, Chang 8 oil layers

Abstract Background Equitable financing is a key objective of health care systems. Its importance is evidenced in policy documents, policy statements, the work of health economists and policy analysts. The conventional categorisations of finance sources for health care are taxation, social health insurance, private health insurance and out-of-pocket payments. There are nonetheless increasing variations in the finance sources used to fund health care. An understanding of the equity implications would help policy makers in achieving equitable financing. Objective The primary purpose of this paper was to comprehensively assess the equity of health care financing in Malaysia, which represents a new country context for the quantitative techniques used. The paper evaluated each of the five financing sources (direct taxes, indirect taxes, contributions to Employee Provident Fund and Social Security Organization, private insurance and out-of-pocket payments) independently, and subsequently by combined the financing sources to evaluate the whole financing system. Methods Cross-sectional analyses were performed on the Household Expenditure Survey Malaysia 1998/99, using Stata statistical software package. In order to assess inequality, progressivity of each finance sources and the whole financing system was measured by Kakwani's progressivity index. Results Results showed that Malaysia's predominantly tax-financed system was slightly progressive with a Kakwani's progressivity index of 0.186. The net progressive effect was produced by four progressive finance sources (in the decreasing order of direct taxes, private insurance premiums, out-of-pocket payments, contributions to EPF and SOCSO) and a regressive finance source (indirect taxes). Conclusion Malaysia's two tier health system, of a heavily subsidised public sector and a user charged private sector, has produced a progressive health financing system. The case of Malaysia exemplifies that policy makers can gain an in depth understanding of the equity impact, in order to help shape health financing strategies for the nation.