Titanium dioxide nanotubes increase purinergic receptor P2Y6 expression and activate its downstream PKCα-ERK1/2 pathway in bone marrow mesenchymal stem cells under osteogenic induction.

Titanium dioxide (TiO2) nanotubes can improve the osseointegration of pure titanium implants, but this exact mechanism has not been fully elucidated. The purinergic receptor P2Y6 is expressed in bone marrow mesenchymal stem cells (BMSCs) and participates in the regulation of bone metabolism. However, it is unclear as to whether P2Y6 is involved in the osteogenic differentiation of BMSCs induced by TiO2 nanotubes. TiO2 nanotubes were prepared on the surface of titanium specimens using the anodizing method and characterized their features. Quantitative reverse transcriptase polymerase chain reaction and western blotting were used to detect the expression of P2Y6, markers of osteogenic differentiation, and PKCα-ERK1/2. A rat femoral defect model was established to evaluate the osseointegration effect of TiO2 nanotubes combined with P2Y6 agonists. The results showed that the average inner diameter of the TiO2 nanotubes increased with an increase in voltage (voltage range of 30-90V), and the expression of P2Y6 in BMSCs could be upregulated by TiO2 nanotubes in osteogenic culture. Inhibition of P2Y6 expression partially inhibited the osteogenic effect of TiO2 nanotubes and downregulated the activity of the PKCα-ERK1/2 pathway. When using in vitro and in vivo experiments, the osteogenic effect of TiO2 nanotubes when combined with P2Y6 agonists was more pronounced. TiO2 nanotubes promoted the P2Y6 expression of BMSCs during osteogenic differentiation and promoted osteogenesis by activating the PKCα-ERK1/2 pathway. The combined application of TiO2 nanotubes and P2Y6 agonists may be an effective new strategy to improve the osseointegration of titanium implants. STATEMENT OF SIGNIFICANCE: Titanium dioxide (TiO2) nanotubes can improve the osseointegration of pure titanium implants, but this exact mechanism has not been fully elucidated. The purinergic receptor P2Y6 is expressed in bone marrow mesenchymal stem cells (BMSCs) and participates in the regulation of bone metabolism. However, it is unclear as to whether P2Y6 is involved in the osteogenic differentiation of BMSCs induced by TiO2 nanotubes. For the first time, this study revealed the relationship between TiO2 nanotubes and purine receptor P2Y6, and further explored its mode of action, which may provide clues as to the regulatory role of TiO2 nanotubes on osteogenic differentiation of BMSCs. These findings will help to develop novel methods for guiding material design and biosafety evaluation of nano implants.

Exploration of various roles of hypoxia genes in osteosarcoma.

Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.

Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report.

Suppurative arthritis has an acute onset and mostly affects old people and children. Recently, the incidence of adult suppurative hip arthritis, as well as its serious consequences, has increased. The deep hip joint and surrounding hypertrophic muscle tissue limit physical examination. Furthermore, they may cause variable and atypical symptoms of suppurative hip arthritis, possibly inducing delayed diagnosis and treatment. This atypical presentation is uncommon, causing delayed diagnosis and treatment, thus worsening the outcomes. We herein report the case of a 58-year-old man with Staphylococcus aureus (S. aureus) septicemia and multiple organ failure due to left pyogenic arthritis of the hip. The patient's early symptoms were extremely atypical given that he only presented hip pain. Moreover, there was no obvious history of trauma or inflammatory manifestations, such as fever or local swelling, and laboratory examination results and imaging findings were atypical. However, the disease progressed rapidly, developing into systemic sepsis within a short period of time followed by multiple organ failure and death. Early diagnosis and effective treatment of S. aureus hip arthritis are essential to avoid poor outcomes.

Peatland Loss in Southeast Asia Contributing to U.S. Biofuel's Greenhouse Gas Emissions.

Land use change (LUC) induced by biofuel production could lead to greenhouse gas (GHG) emissions, which potentially increase biofuel's carbon intensity. Among the sources of LUC-related emissions for soy biodiesel, the contribution from peatland loss to agricultural plantations in Southeast Asia remains uncertain. Here, we analyzed LUC in Malaysia and Indonesia and modeled its impacts on the GHG emissions of soy biodiesel produced in the United States. It shows that oil palm plantations have more than doubled over 2001-2016 and the area of palm-on-peatlands (PoP) has expanded 3.7 times. Over new palm plantations, the share of PoP is about 19% regardless of time and location and the emission factor (EF) for peatland-to-palm conversion is estimated to be 41.5 Mg CO2 ha-1 yr-1. With these updates on PoP and EF, the contribution of peatland loss (0.7-5.1 g CO2e MJ-1) to biodiesel emissions is only 40-65% of previous estimates, which reduces discrepancies among model simulations used by different agencies. Based on emerging evidence on LUC and related carbon changes, our analysis reexamines regional peatland loss and its impacts on LUC emissions modeling and provides new insights into the estimation of LUC impacts on biofuels' carbon intensity.

L-Glutamine alleviates osteoarthritis by regulating lncRNA-NKILA expression through the TGF-ß1/SMAD2/3 signalling pathway.

Osteoarthritis (OA) is a heterogeneous condition characterized by cartilage degradation, subchondral sclerosis, and osteophyte formation, and accompanied by the generation of pro-inflammatory mediators and degradation of extracellular matrix. The current treatment for early OA is focused on the relief of symptoms, such as pain, but this treatment cannot delay the pathological process. L-Glutamine (L-Gln), which has anti-inflammatory and anti-apoptotic effects, is the most abundant amino acid in human blood. However, its role in OA has not been systematically studied. Therefore, the objective of this work was to explore the therapeutic effect and molecular mechanism of L-Gln on OA. In vitro, we found that L-Gln could up-regulate the expression of the long non-coding RNA NKILA, which is regulated by the transforming growth factor-ß1/SMAD2/3 pathway, and inhibit the activity of nuclear factor-κB, thereby decreasing the expression of nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-13 (MMP-13). This led to a reduction in the generation of nitrous oxide, prostaglandin E-2, tumour necrosis factor-α, and degradation of the extracellular matrix (i.e. aggrecan and collagen II) in rat OA chondrocytes. Moreover, intragastric administration of L-Gln reduced the degradation of cartilage tissue and expression of MMP-13 in a rat OA model. L-Gln also relieved the clinical symptoms in some patients with early knee joint OA. These findings highlight that L-Gln is a potential therapeutic drug to delay the occurrence and development of OA.

Intercomparison of global terrestrial carbon fluxes estimated by MODIS and Earth system models.

Earth system models (ESMs) have been widely used to simulate global terrestrial carbon fluxes, including gross primary production (GPP) and net primary production (NPP). Assessment of such GPP and NPP products can be valuable for understanding the efficacy of certain ESMs in simulating the global carbon cycle and future climate impacts. In this work, we studied the model performance of 22 ESMs participating in the fifth and sixth phases of the Coupled Model Intercomparison Project (CMIP5 and CMIP6) by comparing historical GPP and NPP simulations with satellite data from MODIS and further evaluating potential model improvement from CMIP5 to CMIP6. In CMIP6, the average global total GPP and NPP estimated by the 22 ESMs are 16% and 13% higher than MODIS data, respectively. The multi-model ensembles (MME) of the 22 ESMs can fairly reproduce the spatial distribution, zonal distribution and seasonal variations of both GPP and NPP from MODIS. They perform much better in simulating GPP and NPP for grasslands, wetlands, croplands and other biomes than forests. However, there are noticeable differences among individual ESM simulations in terms of overall fluxes, temporal and spatial flux distributions, and fluxes by biome and region. The MME consistently outperforms all individual models in nearly every respect. Even though several ESMs have been improved in CMIP6 relative to CMIP5, there is still much work to be done to improve individual ESM and overall CMIP performance. Future work needs to focus on more comprehensive model mechanisms and parametrizations, higher resolution and more reasonable coupling of land surface schemes and atmospheric/oceanic schemes.

circARL15 Plays a Critical Role in Intervertebral Disc Degeneration by Modulating miR-431-5p/DISC1.

BACKGROUND: Intervertebral disk degeneration (IDD) is a serious public health problem associated with genetic and environmental factors. However, the pathogenic factors involved and the pathological mechanism of this disease still remain enigmatic. METHODS: The associated microarray was downloaded and further analyzed using statistical software R. The competing endogenous RNA (ceRNA) co-expression network was constructed to measure the meaningful correlated expression of differentially expressed genes. We further measured the expression of circARL15/miR-431-5p/DISC1 in IDD tissues. Cell proliferation and apoptosis were detected in NP cells transfected with a circARL15 overexpression plasmid and miR-431-5p mimics. The expression of DISC1 was detected by immunohistochemistry and Western blot analysis. RESULTS: Within the ceRNA network, circARL15 is the most differentially expressed circular RNA. circARL15 was down-regulated in IDD and was negatively correlated with miR-431-5p and positively associated with DISC1. miR-431-5p was found to bind directly to circARL15 and DISC1. circARL15 inhibited nucleus pulposus cell apoptosis but promoted nucleus pulposus cell proliferation by targeting the miR-431-5p/DISC1 signaling pathway. CONCLUSION: circARL15/miR-431-5p/DISC1 is involved in the pathogenesis of IDD, which might be helpful in determining the diagnostic biomarkers and providing potential therapeutic targets for patients with IDD.

Carrying capacity for vegetation across northern China drylands.

Revegetation and afforestation across drylands for establishing sustainable ecosystems requires a comprehensive understanding of the carrying capacity for vegetation (CCV) at the regional scale. To determine the CCV across drylands in northern China, we developed a technical framework based on two measures of leaf area index (LAI): maximum LAI (Max-LAI) and safe LAI (Safe-LAI), and their thresholds, CCVmax and CCVsafe, for six drylands (Horqin, Hulun Buir, Otindag, Mu Us, Tengger, and Junggar) using remote sensing datasets from 2000 to 2014. We also predicted dynamics of CCV of the drylands over the next decade (2015-2024) by establishing optimal prediction models based on environmental factors (temperature, precipitation, potential evapotranspiration, and elevation). According to these models, the Max-LAI threshold (range: 0.36-1.03 m2/m2) and Safe-LAI threshold (0.29-0.70 m2/m2) declined from east to west with decreases in aridity index. Under current climatic variability and anthropogenic disturbances, the CCV in most drylands would have positive increments (approximately 15%), except in the Horqin (approximately -15%) and Tengger (slight changes), during the following decade. This indicates that there is scope for improving vegetation coverage in most drylands, except in the Horqin and Tengger. Our results suggest that revegetation and ecosystem management to prevent ongoing desertification should be carried out at the regional scale. Although it does not account for biocrusts, artificially introduced vegetation, underground water, and other vegetation attributes (e.g., density and biomass), our technical framework and results might nonetheless be valuable in evaluating regional ecological security and guiding vegetation restoration of drylands across northern China.

Weekly Working Hours and Mental Health Status in Different Occupations: Evidence From the 2015 to 2016 California Health Interview Survey.

OBJECTIVE: The aim of this paper was to identify shapes of the curves between weekly working hours (WWH) and mental health status (MHS) and determine WWH for the best MHS in 13 occupations. METHODS: This cross-sectional study applied public data of the 2015 to 2016 California Health Interview Survey. Restricted cubic spline regression was used to determine non-linear trends. RESULTS: A statistically significant nearly V-shaped curve was demonstrated between WWH and MHS in total population, men and management, business and finance occupations. WWH for the best MHS were 42, 45, and 46 hours, respectively. CONCLUSION: These results suggest MHS be susceptible to WWH in total population, men and management, business and finance occupations. WWH for the best MHS for relevant populations could provide evidence for better work hours regulations in California.

Effect and threshold of PM2.5 on population mortality in a highly polluted area: a study on applicability of standards.

For assessing the effect and threshold of PM2.5 on mortality in highly polluted areas and further studying the standard applicability, daily data on meteorological factors, air pollutants, and mortality were obtained in Jinan, China, from 2011 to 2017. A generalized additive model (GAM) and a distributed lag non-linear model (DLNM) were employed to assess the nonlinearity and the hysteresis of associations. We further explored the breakpoints to evaluate the existence of the threshold. The correlation between mortality and PM2.5 was nonlinear. The impact of average PM2.5 on non-accidental mortality (RR = 1.11; 95% CI = 1.06, 1.16), cardiovascular disease (CVD) mortality (RR = 1.17; 95% CI = 1.10, 1.24), and respiratory disease (RD) mortality (RR = 1.17; 95% CI = 1.10, 1.24) reached the highest in the current day (lag 0). The excess risks of PM2.5 at secondary standard level to non-accidental, CVD, and RD mortality are 8.79% (95% CI = 3.84, 13.98), 14.41% (95% CI = 7.79, 21.43), 15.35% (95% CI = 1.76, 30.74), respectively. The saturation points exist in highly polluted areas. Above the saturation points of 247 µg/m3 for non-accidental mortality, 245 µg/m3 for CVD mortality, and 250 µg/m3 for RD mortality, the model of all three relationships presented a harvesting effect. This study underscores the necessity of the ongoing efforts of reducing particulate air pollution and the adjustment of the standards in seriously polluted areas to adapt to regional conditions. At the same time, for highly polluted areas, it is advocated to strengthen personal protection to decrease the saturation point and control the concentration of pollutants as much as possible, which will substantially save more cost that benefits the public.

Different-shaped curves for serum uric acid with and without diabetes: Results from China Health and Retirement Longitudinal Study.

BACKGROUND: Several studies have revealed conflicting results regarding the relationship between serum uric acid (SUA) and blood glucose concentrations. The aim of this study was to identify the shape of the curve between SUA and either fasting plasma glucose (FPG) or HbA1c in diabetic and non-diabetic participants. METHODS: This cross-sectional study of the relationship between SUA and diabetes and non-diabetes was conducted in 10 266 participants. Data from the national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS; 2011-12) were used. Restrictive cubic spline regression and two piecewise linear regression models were used to detect non-linear trends and calculate the slope of each segment. RESULTS: After adjusting for all confounding factors in all subjects, an L-shaped relationship was found between FPG and SUA in males (ß2 = 3.47, P < 0.01) and females (ß2 = 5.84, P < 0.01), as well as between HbA1c and SUA in males (ß2 = 0.10, P = 0.03) and females (ß2 = 0.12, P = 0.02). In non-diabetic individuals, there was a positive linear correlation between FPG and SUA in females (ß = 0.62, P = 0.02). After a diagnosis of diabetes, a negative linear relationship was found between SUA and blood glucose in males, and a nearly L-shaped curve was found in females. CONCLUSIONS: An L-shaped association was found between SUA and blood glucose in both genders. Stratified analysis revealed an L-shaped curve only in diabetic females. Further studies are warranted to investigate the mechanisms of the association between uric acid and blood glucose levels.