Associations of Urinary Heavy Metal Mixtures with High Remnant Cholesterol among US Adults: Evidence from the National Health and Nutrition Examination Survey (1998-2018).

The main objective of our study is to explore the associations between combined exposure to urinary heavy metals and high remnant cholesterol (HRC), a known cardiovascular risk factor. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we conducted a cross-sectional analysis of 5690 participants, assessing urinary concentrations of ten heavy metals. Ten heavy metals in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Fasting residual cholesterol ≥0.8 mmol/L was defined as HRC (using blood samples). Statistical analyses included weighted multivariable logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the associations of heavy metal exposure with HRC. Stratified analyses based on individual characteristics were also conducted. Multivariable logistic regression found that the four metals (OR Q4 vs. Q1: 1.33, 95% CI: 1.01-1.75 for barium (Ba); OR Q4 vs. Q1: 1.50, 95% CI: 1.16-1.94 for cadmium (Cd); OR Q4 vs. Q1: 1.52, 95% CI: 1.15-2.01 for mercury (Hg); OR Q4 vs. Q1: 1.35, 95% CI: 1.06-1.73 for lead (Pb)) were positively correlated with the elevated risk of HRC after adjusting for covariates. In addition, all three mixed models, including WQS (OR: 1.25; 95% CI: 1.07-1.46), qgcomp (OR: 1.17; 95% CI: 1.03-1.34), and BKMR, consistently showed a significant positive correlation between co-exposure to heavy metal mixtures and HRC, with Ba and Cd being the main contributors within the mixture. These associations were more pronounced in younger adults (20 to 59 years), males, and those with a higher body mass index status (≥25 kg/m2). Our findings reveal a significant relationship between exposure to the mixture of heavy metals and HRC among US adults, with Ba and Cd being the major contributors to the mixture's overall effect. Public health efforts aimed at reducing heavy metal exposure can help prevent HRC and, in turn, cardiovascular disease.

Associations of Combined Exposure to Metabolic and Inflammatory Indicators with Thyroid Nodules in Adults: A Nested Case-Control Study.

Objective: To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods: We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results: In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07-1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08-1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04-1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02-1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07-1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61-0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions: Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

Transport Anisotropy in One-Dimensional Graphene Superlattice in the High Kronig-Penney Potential Limit.

One-dimensional graphene superlattice subjected to strong Kronig-Penney (KP) potential is promising for achieving the electron-lensing effect, while previous studies utilizing the modulated dielectric gates can only yield a moderate, spatially dispersed potential profile. Here, we realize high KP potential modulation of graphene via nanoscale ferroelectric domain gating. Graphene transistors are fabricated on PbZr_{0.2}Ti_{0.8}O_{3} back gates patterned with periodic, 100-200 nm wide stripe domains. Because of band reconstruction, the h-BN top gating induces satellite Dirac points in samples with current along the superlattice vector s[over ^], a feature absent in samples with current perpendicular to s[over ^]. The satellite Dirac point position scales with the superlattice period (L) as ∝L^{ß}, with ß=-1.18±0.06. These results can be well explained by the high KP potential scenario, with the Fermi velocity perpendicular to s[over ^] quenched to about 1% of that for pristine graphene. Our study presents a promising material platform for realizing electron supercollimation and investigating flat band phenomena.

Short-term effects of heatwaves on clinical and subclinical cardiovascular indicators in Chinese adults: A distributed lag analysis.

AIMS: Previous studies have related heat waves to morbidity and mortality of cardiovascular diseases; however, potential mechanisms remained limited. Our aims were to investigate the short-term effects of heat waves on a series of clinical/subclinical indicators associated with cardiovascular health. METHODS: Our study used 80,574 health examination records from the Health Management Center of Nanjing Zhongda Hospital during the warm seasons of 2019-2021, including 62,128 participants. A total of 11 recognized indicators of cardiovascular risk or injury were assessed. Air pollution and meteorological data were obtained from the Nanjing Ecological Environment Bureau and the China Meteorological Data Network, respectively. Heat waves were defined as a daily average temperature over the 95th percentile for three or more consecutive days from May to September. We used a combination of linear mixed effects models and distributed lag nonlinear models to assess the lagged effects of heat waves on clinical and subclinical cardiovascular indicators. Stratified analyses based on individuals' characteristics, including gender, age, body mass index (BMI), diabetes, and hypertension, were also performed. RESULTS: Heat waves were related to significant changes in most indicators, with the magnitude of effects generally peaking at a lag of 0 to 3 days. Moreover, the cumulative percentage changes over lag 0-7 days were -0.82 % to -2.55 % in blood pressure, 1.32 % in heart rate, 0.20 % to 2.66 % in systemic inflammation markers, 0.36 % in a blood viscosity parameter, 9.36 % in homocysteine, and 1.35 % to 3.25 % in injuring myocardial enzymes. Interestingly, females and males showed distinct susceptibilities in different indicators. Stronger effects were also found in participants aged 50 years or over, individuals with abnormal BMI status, and patients with diabetes. CONCLUSION: Short-term exposure to heat waves could significantly alter clinical/subclinical cardiovascular indicator profiles, including blood pressure changes, increased heart rate, acute systemic inflammation, elevated blood viscosity, and myocardial injury.

HRBUST-LLPED: A Benchmark Dataset for Wearable Low-Light Pedestrian Detection.

Detecting pedestrians in low-light conditions is challenging, especially in the context of wearable platforms. Infrared cameras have been employed to enhance detection capabilities, whereas low-light cameras capture the more intricate features of pedestrians. With this in mind, we introduce a low-light pedestrian detection (called HRBUST-LLPED) dataset by capturing pedestrian data on campus using wearable low-light cameras. Most of the data were gathered under starlight-level illumination. Our dataset annotates 32,148 pedestrian instances in 4269 keyframes. The pedestrian density reaches high values with more than seven people per image. We provide four lightweight, low-light pedestrian detection models based on advanced YOLOv5 and YOLOv8. By training the models on public datasets and fine-tuning them on the HRBUST-LLPED dataset, our model obtained 69.90% in terms of AP@0.5:0.95 and 1.6 ms for the inference time. The experiments demonstrate that our research can assist in advancing pedestrian detection research by using low-light cameras in wearable devices.

Trichostatin A enhances the titanium rods osseointegration in osteoporotic rats by the inhibition of oxidative stress through activating the AKT/Nrf2 pathway.

The use of titanium implants as fixed supports following fractures in patients with OP can often result in sterile loosening and poor osseointegration. Oxidative stress has been shown to play a particularly important role in this process. While TSA has been reported to facilitate in vivo osteogenesis, the underlying mechanisms remain to be clarified. It also remains unclear whether TSA can improve the osseointegration of titanium implants. This study investigated whether TSA could enhance the osseointegration of titanium rods by activating AKT/Nrf2 pathway signaling, thereby suppressing oxidative stress. MC3T3-E1 cells treated with CCCP to induce oxidative stress served as an in vitro model, while an OVX-induced OP rat model was employed for in vivo analysis of titanium rod implantation. In vitro, TSA treatment of CCCP-treated MC3T3-E1 cells resulted in the upregulation of osteogenic proteins together with increased AKT, total Nrf2, nuclear Nrf2, HO-1, and NQO1 expression, enhanced mitochondrial functionality, and decreased oxidative damage. Notably, the PI3K/AKT inhibitor LY294002 reversed these effects. In vivo, TSA effectively enhanced the microstructural characteristics of distal femur trabecular bone, increased BMSCs mineralization capacity, promoted bone formation, and improved the binding of titanium implants to the surrounding tissue. Finally, our results showed that TSA could reverse oxidative stress-induced cell damage while promoting bone healing and improving titanium rods' osseointegration through AKT/Nrf2 pathway activation.

Particle size distribution measurement based on the angular scattering efficiency factor spectra inversion-simulation and experiment.

The quantification of the particle size distribution (PSD) within a particle system is significant to various domains, including atmospheric and environmental sciences, material science, civil engineering, and human health. The scattering spectrum reflects the PSD information of the particle system. Researchers have developed high-precision and high-resolution PSD measurements for monodisperse particle systems through scattering spectroscopy. However, for polydisperse particle systems, current methods based on light scattering spectrum and Fourier transform analysis can only obtain the information of the particle component, but cannot provide the relative content information of each component. In this paper, a PSD inversion method based on the angular scattering efficiency factors (ASEF) spectrum is proposed. By establishing a light energy coefficient distribution matrix, and then measuring the scattering spectrum of the particle system, PSD can be measured in conjunction with inversion algorithms. The simulations and experiments conducted in this paper substantiate the validity of the proposed method. Unlike the forward diffraction approach that measures the spatial distribution of scattered light I(θ) for inversion, our method uses the multi-wavelength distribution information of scattered light ß(λ). Moreover, the influences of noise, scattering angle, wavelength, particle size range, and size discretization interval on PSD inversion are studied. The method of condition number analysis is proposed to identify the appropriate scattering angle, particle size measurement range, and size discretization interval, and it can reduce the root mean square error(RMSE) of PSD inversion. Furthermore, the method of wavelength sensitivity analysis is proposed to select the spectral band with higher sensitivity to particle size changes, thereby improving the computational speed and avoiding the problem of diminished accuracy caused by the reduction of the number of wavelengths used.

Short-term effects of cold spells on hematocrit among adults in Nanjing, China: A distributed-lagged effect analysis.

BACKGROUND: Previous studies have linked exposure to cold spells with cardiovascular diseases, however, underlying mechanisms remained to be understood. We aimed to explore the short-term effects of cold spells on hematocrit, a blood indicator associated with cardiovascular disease. METHODS: Our study was performed among 50,538 participants (68,361 health examination records) who visited the health examination centers of Zhongda Hospital in Nanjing City, China, during the cold seasons from 2019 to 2021. Data on meteorology and air pollution were obtained from the China Meteorological Data Network and the Nanjing Ecological Environment Bureau, respectively. Cold spells in this study were defined as daily mean temperatures (Tmean) <3rd or 5th percentile with two or more consecutive days. Linear mixed-effect models combined with distributed lag nonlinear models were applied to estimate associations of cold spells with hematocrit. RESULTS: Cold spells were found to be significantly correlated with increased hematocrit on lag 0 to 26 days. Moreover, the cumulative effects of cold spells on hematocrit remained significant at varying lag days. These single and cumulative effects were robust across different definitions of cold spells and conversions of hematocrit. For instance, cold spells (Tmean <3rd percentile) at lags 0, 0-1, and 0-27 days were significantly associated with 0.09 [95 % confidence interval (CI): 0.03, 0.15], 0.17 (95 % CI: 0.07, 0.28), and 3.71 (95 % CI: 3.06, 4.35) - unit (%) increases in original hematocrit, respectively. In subgroup analyses, stronger effects of cold spells on hematocrit were observed in females and participants aged 50 years or over. CONCLUSION: Cold spells have significant immediate and longer-lagged effects (up to 26 days) on hematocrit. Females and individuals aged 50 years or over are more sensitive to cold spells. These findings might provide a new perspective for exploring the effects of cold spells on adverse cardiac events.

Electronic structure engineering on NiSe2 micro-octahedra via nitrogen doping enabling long cycle life magnesium ion batteries.

Multivalent ion batteries have attracted great attention because of their abundant reserves, low cost and high safety. Among them, magnesium ion batteries (MIBs) have been regarded as a promising alternative for large-scale energy storage device owing to its high volumetric capacities and unfavorable dendrite formation. However, the strong interaction between Mg2+ and electrolyte as well as cathode material results in very slow insertion and diffusion kinetics. Therefore, it is highly necessary to develop high-performance cathode materials compatible with electrolyte for MIBs. Herein, the electronic structure of NiSe2 micro-octahedra was modulated by nitrogen doping (N-NiSe2) through hydrothermal method followed by a pyrolysis process and this N-NiSe2 micro-octahedra was used as cathode materials for MIBs. It is worth noting that N-NiSe2 micro-octahedra shows more redox active sites and faster Mg2+ diffusion kinetics compared with NiSe2 micro-octahedra without nitrogen doping. Moreover, the density functional theory (DFT) calculations indicated that the doping of nitrogen could improve the conductivity of active materials on the one hand, facilitating Mg2+ ion diffusion kinetics, and on the other hand, nitrogen dopant sites could provide more Mg2+ adsorption sites. As a result, the N-NiSe2 micro-octahedra cathode exhibits a high reversible discharge capacity of 169 mAh g-1 at the current density of 50 mA g-1, and a good cycling stability over 500 cycles with a maintained discharge capacity of 158.5 mAh g-1. This work provides a new idea to improve the electrochemical performance of cathode materials for MIBs by the introduction of heteroatom dopant.

Ultrafast electron diffraction instrument for gas and condensed matter samples.

We report the modification of a gas phase ultrafast electron diffraction (UED) instrument that enables experiments with both gas and condensed matter targets, where a time-resolved experiment with sub-picosecond resolution is demonstrated with solid state samples. The instrument relies on a hybrid DC-RF acceleration structure to deliver femtosecond electron pulses on the target, which is synchronized with femtosecond laser pulses. The laser pulses and electron pulses are used to excite the sample and to probe the structural dynamics, respectively. The new system is added with capabilities to perform transmission UED on thin solid samples. It allows for cooling samples to cryogenic temperatures and to carry out time-resolved measurements. We tested the cooling capability by recording diffraction patterns of temperature dependent charge density waves in 1T-TaS2. The time-resolved capability is experimentally verified by capturing the dynamics in photoexcited single-crystal gold.

Daytime administration of melatonin has better protective effects on bone loss in ovariectomized rats.

OBJECTIVE: To explore the difference in the protective effects of intraperitoneal injection of exogenous melatonin of daytime or nighttime on bone loss in ovariectomized (OVX) rats. METHODS: After bilateral ovariectomy and sham surgery, 40 rats were randomly divided into four groups: sham operation group (Sham), ovariectomy (OVX), and daytime melatonin injection group (OVX + DMLT, 9:00, 30 mg/kg/d) and nighttime injection of melatonin (OVX + NMLT, 22:00, 30 mg/kg/d). After 12 weeks of treatment, the rats were sacrificed. The distal femur, blood and femoral marrow cavity contents were saved. The rest of the samples were tested by Micro-CT, histology, biomechanics and molecular biology. Blood was used for bone metabolism marker measurements. CCK-8, ROS, and Cell apoptosis are performed using MC3E3-T1 cells. RESULTS: Compared with treatment at night, the bone mass of the OVX rats was significantly increased after the daytime administration. All microscopic parameters of trabecular bone increased, only Tb.Sp decreased. Histologically, the bone microarchitecture of the OVX + DMLT was also more dense than the bone microarchitecture of the OVX + LMLT. In the biomechanical experiment, the femur samples of the day treatment group were able to withstand greater loads and deformation. In molecular biology experiments, bone formation-related molecules increased, while bone resorption-related molecules decreased. After treatment with melatonin administration at night, the expression of MT-1ß was significantly decreased. In cell experiments, the MC3E3-T1 cells treated with low-dose MLT had higher cell viability and greater efficiency in inhibiting ROS production than the MC3E3-T1 cells treated with high-dose MLT, which in turn more effectively inhibited apoptosis. CONCLUSION: Daytime administration of melatonin acquires better protective effects on bone loss than night in OVX rats.

Co-modified 3D printed ß-tricalcium phosphate with magnesium and selenium promotes bone defect regeneration in ovariectomized rat.

Magnesium (Mg) and Selenium (Se) are essential elements for bone health and have been studied extensively for its powerful osteogenesis and promoting bone regeneration. The purpose was to observe whether Co-modified 3D-printed ß-tricalcium phosphate with Mg and Se could promote bone defect regeneration in an ovariectomized(OVX) rat model. The MC3T3-E1 cells were co-cultured with the leachate of ß-TCP, Mg-TCP, and Mg/Se-TCP and induced to osteogenesis, and the cell viability, ROS, and osteogenic activity were observed by Cell Count Kit-8(CCK-8), fluorescent probe 2', 7'-dichlorofluorescin diacetate, Alkaline phosphatase (ALP) staining, Alizarin Red(RES) staining, western blotting(WB), and immunofluorescence. Then the ß-TCP, Mg-TCP, and Mg/Se-TCP were implanted into the femoral epiphysis bone defect model of OVX rats for 12 weeks. Micro-CT and histology analysis were used to observe the therapeutic effect. In vitro results show that the cell mineralization and osteogenic activity of the Mg/Se-TCP group is significantly higher than the ß-TCP group and Mg-TCP group. Protein expressions such as FOxO1, SIRT1, SOD2, Runx-2, Cola1a, and OC of the Mg/Se-TCP group are significantly higher than the Con group and the ß-TCP group. The results of intracellular ROS and SIRT1 and SOD2 immunofluorescence showed that Mg/Se-TCP can restore the oxidative stress balance of osteoblasts. Micro-CT and histology analysis showed that treatment with Mg/Se-TCP showed the largest amount of bone tissue in the defect area (p < 0.05), and exhibited lower values of residual biological material (p < 0.05), compared to that of the ß-TCP group and Mg-TCP group. Our research results confirm that Mg/Se-TCP can improve the activity and function of osteoblasts and enhance bone regeneration mediated by reducing intracellular ROS in OVX rat models. The release of Mg and Se during the degradation of Mg/Se-TCP can improve the local bone repair ability. At the same time, it can also inhibit cell ROS, and ultimately greatly promote local bone repair.

MgAl Saponite as a Transition-Metal-Free Anode Material for Lithium-Ion Batteries.

Transition-metal compounds (oxides, sulfides, hydroxides, etc.) as lithium-ion battery (LIB) anodes usually show extraordinary capacity larger than the theoretical value due to the transformation of LiOH into Li2O/LiH. However, there has rarely been a report relaying the transformation of LiOH into Li2O/LiH as the main reaction for LIBs, due to the strong alkalinity of LiOH leading to battery deterioration. In this work, layered silicate MgAl saponite (MA-SAP) is applied as a -OH donor to generate LiOH as the anode material of LIBs for the first time. The MA-SAP maintains a layered structure during the (dis)charging process and has zero-strain characteristic on the (001) crystal plane. In the discharging process, Mg, Al, and Si in the saponite sheets become electron-rich, while the active hydroxyl groups escape from the sheets and combine with lithium ions to form LiOH in the "caves" on sheets, and the LiOH continues to decompose into Li2O and LiH. Consequently, the MA-SAP delivers a maximum capacity of 536 mA h·g-1 at 200 mA·g-1 with a good high-current discharging ability of 155 mA h·g-1 after 1000 cycles under 1 A·g-1. Considering its extremely low cost and completely nontoxic characteristics, MA-SAP has great application prospects in energy storage. In addition, this work has an enlightening effect on the development of new anodes based on extraordinary mechanisms.

Aloe polysaccharide promotes osteogenesis potential of adipose-derived stromal cells via BMP-2/Smads and prevents ovariectomized-induced osteoporosis.

BACKGROUND: Aloe polysaccharide (AP) is a type of an active macromolecule of Aloe vera, which contributes to its function. However, whether AP possesses anti-osteoporosis properties is unknown. METHODS: Adipose-derived stromal cells were treated with different concentrations of AP. Early and late osteogenesis were, respectively, evaluated by ALP and Alizarin Red S staining. The effect of AP on the processes of adipogenesis inhibition in ADSCs was analyzed by oil red O staining. Western blot was used to assess the expression of osteogenic and adipogenic related factors. Then, Noggin was administered to further confirm the mechanism by which AP promotes the osteogenesis of ADSCs. Finally, 40 female SD rats were classified into a bilateral laparotomy group (Sham group) and three bilateral ovariectomy groups: OVX group, OVX + AP group, and OVX + AP + Noggin group. The bilateral rat femurs were collected to perform micro-CT scanning, HE, Masson trichrome, and Oil red O staining. RESULTS: The results indicated that AP could increase ALP expression and calcium deposition. Through molecular mechanisms, AP promotes the protein expression of COL1A1, OPN, and ALP in ADSCs, but downregulates the expression of PPARγ. Also, AP directs ADSCs' fate by stimulating the BMP2/Smads signaling pathway. In vivo, the rat AP-treated had more trabecular bone than the OVX rat, indicating partial protection from cancellous bone loss after treatment with AP. CONCLUSION: Our results show that AP may promote osteogenesis of ADSCs through BMP-2/Smads signaling pathway and inhibits lipogenic differentiation. Thus, AP might be a promising alternative medicine to treat postmenopausal osteoporosis.

Silibinin-modified Hydroxyapatite coating promotes the osseointegration of titanium rods by activation SIRT1/SOD2 signaling pathway in diabetic rats.

The purpose of this study is to investigate the role of Silibinin (SIL)-modified Hydroxyapatite coating on osseointegration in diabetes in vivo and in vitro and explore the mechanism of osteogenic differentiation of MC3T3-E1. RT-qPCR, Immunofluorescence, and Western blot were used to measure the expression level of oxidative Stress Indicators and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability in hyperglycemia. Alizarin red staining and alkaline phosphatase staining were used to examine osteogenic function and calcium deposits. The diabetic rat model receive titanium rod implantation was set up successfully and Von-Gieson staining was used to examine femoral bone tissue around titanium rod. Our results showed that intracellular oxidative stress in hyperglycemia was overexpressed, while FoxO1, SIRT1, GPX1, and SOD2 were downregulated. SIL suppressed oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that SIL promoted osteogenic differentiation of MC3T3-E1 and obviously restored the osseointegration ability of diabetic rats. Further study indicated that SIL exerted its beneficial function through activation SIRT1/SOD2 signaling pathway to restore osteoblast function, and improved the osseointegration and stability of titanium rods in vivo. Our research suggested that the SIL-modulated oxidative Stress inhibition is responsible for the activation of the process of osteogenic differentiation through activation SIRT1/SOD2 signaling pathway in hyperglycemia, providing a novel insight into improving prosthetic osseointegration in diabetic patients. Hyperglycemia impaired the activity and function of MC3T3-E1 and inhibits bone formation by up-regulating intracellular ROS levels through inhibition of SIRT1/SOD2 signaling pathway. Local administrator SIL can improve the activity and function of osteoblasts and enhance osseointegration by reducing intracellular ROS through activation of SIRT1/SOD2 signaling pathway in DM rat models.

Silymarin prevents iron overload induced bone loss by inhibiting oxidative stress in an ovariectomized animal model.

Silibinin (SIL) has been used extensively for its hepatoprotective properties and antioxidant properties, including bone health. Iron overload can inhibit osteogenic proliferation and differentiation and promote bone loss. However, whether SIL can reverse the harmful effects of iron overload inovariectomized (OVX) rats and the mechanism is not clear. Therefore, this study intends to investigate the effect of SIL on bone mass and bone metabolism in iron overload rats and also explore the role of SIL on osteogenic differentiation of MC3T3-E1.RT-qPCR was used to measure the transcribe of target genes. Furthermore, alizarin red staining, alkaline phosphatase staining, immunofluorescence and CCK-8 assay were conducted to detect cell viability and target protein expression, osteogenic function. The OVX rat model with iron overload was set up to investigate bone reconstruction.Our results demonstrated that SIL promotes the proliferation and differentiation of osteoblasts, increases the ALP secretion and mineralization ability of osteoblasts, and enhances the transcribe and expression of target genes including OC, Runx-2, SOD2 and SIRT1 in an iron overload environment. In addition, it was confirmed that systemic SIL administration inhibits bone loss in OVX rats with iron overload and changes bone metabolism and oxidative stress status. Further study has shown that iron overload exerts its harmful function by accelerating bone turnover-mediated changes in higher bone metabolism to worsen osteoporosis. SIL can inhibit the unfriendly effects of iron overload, and by modifying bone metabolism and oxidative stress levels, the results contribute to clinical prevention and treatment of the progression of postmenopausal osteoporosis.

[Comparison of curative effect between F-shaped hollow screw and traditional three parallel screws in the treatment of Pauwels type â ¢ femoral neck fracture].

OBJECTIVE: To analyze and compare the clinical efficacy of F-shaped hollow screw and traditional inverted triangle three parallel screws in the treatment of young and middle-aged Pauwels type Ⅲ femoral neck fracture. METHODS: From January 2017 to January 2020, 38 patients with Pauwels type Ⅲ femoral neck fracture were treated. They were divided into two groups according to different screw placement methods. Among them, 18 patients in group A were fixed with F-shaped hollow screw, including 12 males and 6 females, aged 37 to 55 years, the time from injury to operation was 1 to 3 days. Other 20 cases in group B were fixed with 3 parallel screws in traditional inverted triangle, including 12 males and 8 females, aged 35 to 55 years. The time from injury to operation was 1 to 3 days. The fracture nonunion, femoral head necrosis, femoral neck shortening, hollow screw withdrawal, hip function Harris score and visual analogue scale(VAS) of pain were compared between the two groups. RESULTS: All patients were followed up for 15 to 31 months. There was no significant difference in fracture nonunion, femoral neck shortening and femoral head necrosis between two groups(P>0.05). There was significant difference in screw withdrawal between two groups(P<0.05). There was no significant difference in hip Harris score and VAS between the two groups at 12 months after operation(P>0.05). CONCLUSION: The short-term and medium-term effects of F-shaped and traditional inverted triangle three parallel screws in the treatment of young and middle-aged Pauwels Ⅲ femoral neck fractures are similar, but the nail withdrawal rate of F-shaped hollow screw is low.

Probucol promotes osteoblasts differentiation and prevents osteoporosis development through reducing oxidative stress.

Probucol (PBC) is a potent cholesterol-lowering drug and has been studied extensively for its powerful antioxidative stress. The purpose of this study is to investigate the role of PBC in ovariectomized rat model and to explore the mechanism of osteogenic differentiation of MC3TE-E1 Cells. RT-qPCR and Immunofluorescence were used to measure the expression level of SOD2, SIRT1, intracellular oxidative stress levels and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability. Alizarin red staining and alkaline phosphatase staining were applied to examine osteogenic function and calcium deposits. The ovariectomized rat model was set up successfully and HE staining were employed to examine femoral trabeculae tissue. Our results showed that PBC suppressed MC3TE-E1 resist oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that PBC promoted osteogenic differentiation of MC3TE-E1 through inhibiting oxidative stress. Further study indicated that PBC exerted its beneficial function by suppressing oxidative stress-mediated alter bone metabolism to alleviate osteoporosis in vivo. Our research suggested that the PBC-modulated oxidative stress inhibition is responsible for activation of the process of osteogenic differentiation, providing a novel insight into the treatment of osteoporosis.

Melatonin alleviates hydrogen peroxide induced oxidative damage in MC3T3-E1 cells and promotes osteogenesis by activating SIRT1.

Oxidative stress is an important contributor to the development of osteoporosis. Melatonin, an indoleamine secreted by the pineal gland, has antioxidant properties. This study aims to explore whether melatonin can promote bone formation and elucidate the mechanisms underlying this process. In this study, we used an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in MC3T3-E1 cells and an in vivo ovariectomized osteoporotic bone defect model in rats to explore the protective effects of melatonin against osteoporotic bone defects along with the mechanism underlying these effects. We found that melatonin significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of BMP2, RUNX2, and OPN in MC3T3-E1 cells treated with H2O2. Furthermore, melatonin was found to activate SIRT1, SIRT3 and inhibit p66Shc, reduce the intracellular reactive oxygen species levels, stabilize mitochondria, reduce malondialdehyde levels, increase superoxide dismutase activity, and reduce apoptosis in MC3T3-E1 cells treated with H2O2. Intriguingly, these effects could be reversed by the SIRT1 inhibitor EX527. In vivo experiments confirmed that melatonin improves the microstructure and bone mineral density of the distal femoral bone trabecula and promotes bone formation. Meanwhile, melatonin activated SIRT1, inhibited p66Shc and increased SIRT3 expression. Taken together, our findings showed that melatonin can restrain oxidative damage in MC3T3-E1 cells and promote osteogenesis by activating SIRT1 which regulate the activity of SIRT3 and inhibit the expression of p66Shc, suggesting that melatonin could be a potential therapeutic agent for osteoporosis-related bone metabolic diseases.

Silibinin Can Promote Bone Regeneration of Selenium Hydrogel by Reducing the Oxidative Stress Pathway in Ovariectomized Rats.

Osteoporosis-related bone defects are a major public health concern. Considering poor effects of a singular pharmacological treatment, many have sought combination therapies, including local treatment combined with systemic intervention. Based on recent evidence that selenium and silibinin increase bone formation and bone mineral density, it is hypothesized that systemic administration with silibinin plus local treatment with selenium may have an additive effect on bone regeneration in an OVX rat model with bone defects. To verify this hypothesis, 3-month-old ovariectomized Sprague- Dawley rats (n = 10/gp) were intraperitoneally with a dose of 50 mg/kg silibinin with selenium hydrogel scaffolds implanted into femoral metaphysis bone defect. Moreover, the MC3T3-E1 cells were co-cultured with selenium and silibinin, and observed any change of cell viability, ROS, and osteogenic activity. Experiment results show that the cell mineralization and osteogenic activity of silibinin plus selenium (SSe) group is enormously higher than the control (Con) group and selenium (Se) group, while ROS appears to be immensely reduced. Osteogenic protein expressions such as SIRT1, SOD2, RUNX-2 and OC of SSe group are significantly higher than Con group and Se group. Micro-CT and Histological analysis evaluation display that group SSe, compared with Con group and Se group, presents the strongest effect on bone regeneration, bone mineralization and higher expression of SIRT1 and SOD2. RT-qPCR analysis indicates that SSe group manifests increased SIRT1, SOD1, SOD2 and CAT than the Con group and Se group (p < 0.05). Our current study demonstrates that systemic administration with SIL plus local treatment with Se is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved via reducing the oxidative stress pathway.