Summary Objective To investigate changes in bone structure, turnover, and articular cartilage localized in subchondral bone cyst (SBC) regions associated with knee osteoarthritis (OA). Methods Tibial ...plateaus ( n = 97) were collected from knee OA patients during total knee arthroplasty (TKA). SBCs were identified using micro-computed tomography, and the specimens were divided into non-cyst ( n = 25) and bone cyst ( n = 72) groups. Microstructure of subchondral bone was assessed using bone volume fraction (BV/TV), trabecular number (Tb.N), structure model index (SMI) and bone mineral density (BMD). In bone cyst group, the cyst subregion, which contained at least one cyst, and the peri-cyst subregion, which contained no cysts, were further selected for microstructure analysis. Articular cartilage damage was estimated using the Osteoarthritis Research Society International (OARSI) score. The numbers of TRAP+ osteoclasts, Osterix+ osteoprogenitors, Osteocalcin+ osteoblasts and expression of SOX9 were evaluated by immunohistochemistry. Results Bone cyst group presented higher BV/TV, Tb.N and SMI at subchondral bone than non-cyst group. Furthermore, cyst subregion displayed increased BV/TV and Tb.N but lower BMD and SMI than peri-cyst subregion. Histology revealed a higher OARSI score in bone cyst group. SBC exhibited a weak relationship with BV/TV, etc . The numbers of TRAP+ osteoclasts, Osterix+ osteoprogenitors, Osteocalcin+ osteoblasts and expression of SOX9, were higher in bone cyst group. Conclusion SBCs within knee OA are characterized by focally increased bone turnover, altered bone structure and more severe articular cartilage damage. The increased bone turnover possibly contributes to altered bone structure localized in SBC areas, and thus aggravates articular cartilage degeneration.
Laser powder bed fusion (LPBF) has proved to be a promising process for tuning the microstructure and mechanical response in NiTi-shaped memory alloys using a varied energy density input by modifying ...the process parameters such as laser power or scanning speed. The microstructure, precipitation, chemical composition, and their relationship with austenite–martensite transformation temperatures (TTs) and superelastic properties have been extensively investigated in Ni-rich NiTi alloys processed at varying volume energy densities (52–110 J/mm3) through LPBF. A specific amount of Ni3Ti precipitation was observed and primarily located along the boundary and at the center of the melt pool, and nanoscale spherical NiTi2/Ni2Ti4OX precipitation was homogeneously dispersed in the B2 matrix and B19’ martensite, but no Ni4Ti3 was observed as frequently reported in the literature. Decreasing the volume energy density (VED) led to lower TTs and a higher recovery strain ratio. However, there is an exception for the sample built with the highest laser power of 250 W that possesses the largest Ni/Ti atomic ratio and therefore the highest superelastic property despite the mediated VED (∼87 J/mm3) employed. We concluded that the variation in TTs and superelastic properties among the samples is caused by the varying amounts of Ni, which causes competition among alloying elements in evaporation, condensation, and precipitation during LPBF.
•Lower energy density reduces TTs except for high laser power of 250 W.•Ni3Ti occurs along the boundary and center of the melt pool.•Nanoscale NiTi2/Ni2Ti4OX is dispersed in B2 and B19′ phases.•The high superelastic property corresponds to low TTs.•TTs depends on net effect of element evaporation, condensation and precipitation.
Ketosis is one of the most prevalent and complex metabolic disorders in high-producing dairy cows and usually detected through analyses of β-hydroxybutyrate (BHB) concentration in blood. Our main ...objectives were to evaluate genetic parameters for blood BHB predicted based on Fourier-transform mid-infrared spectra from 5 to 305 d in milk, and estimate the genetic relationships of blood BHB with 7 reproduction traits and 6 longevity traits in Holstein cattle. Predicted blood BHB records of 11,609 Holstein cows (after quality control) were collected from 2016 to 2019 and used to derive 4 traits based on parity number, including predicted blood BHB in all parities (BHBp), parity 1 (BHB1), parity 2 (BHB2), and parity 3+ (BHB3). Single- and multitrait repeatability models were used for estimating genetic parameters for the 4 BHB traits. Random regression test-day models implemented via Bayesian inference were used to evaluate the daily genetic feature of BHB variability. In addition, genetic correlations were calculated for the 4 BHB traits with reproduction and longevity traits. The heritability estimates of BHBp, BHB1, BHB2, and BHB3 ranged from 0.100 ± 0.026 (± standard error) to 0.131 ± 0.023. The BHB in parities 1 to 3+ were highly genetically correlated and ranged from 0.788 (BHB1 and BHB2) to 0.911 (BHB1 and BHB3). The daily heritability of BHBp ranged from 0.069 to 0.195, higher for the early and lower for the later lactation periods. A similar trend was observed for BHB1, BHB2, and BHB3. There are low direct genetic correlations between BHBp and selected reproductive performance and longevity traits, which ranged from −0.168 ± 0.019 (BHBp and production life) to 0.157 ± 0.019 (BHBp and age at first calving) for the early lactation stage (5 to 65 d). These direct genetic correlations indicate that cows with higher BHBp (greater likelihood of having ketosis) in blood usually have shorter production life (−0.168 ± 0.019). Cows with higher fertility and postpartum recovery, such as younger age at first calving (0.157 ± 0.019) and shorter interval from calving to first insemination in heifer (0.111 ± 0.006), usually have lower BHB concentration in the blood. Furthermore, the direct genetic correlations change across parity and lactation stage. In general, our results suggest that selection for lower predicted BHB in early lactation could be an efficient strategy for reducing the incidence of ketosis as well as indirectly improving reproductive and longevity performance in Holstein cattle.
Woody plants faced multiple abiotic stresses in forest plantation that can influence their growth and development. Dalbergia odorifera T. Chen is a vulnerably endangered tree species, and references ...about its responses to abiotic stresses are very rare in literature. Furthermore, the mechanisms underlying the abiotic stress tolerance in plants induced by exogenous glycine betaine (GB) remains unclear. Indeed, the alternative oxidase (AOX) is one of the major components of antioxidant enzymatic machinery, and there are no studies that focused on the effects of GB on the amount of AOX protein in plants under drought or cold stresses. Thus, the aim of this study was to investigate the effect of exogenous GB on the phenotype, osmoprotectants, photosynthetic pigments, and antioxidant systems in D. odorifera under cold and drought stresses. The layout of the trial was a factorial experiment in a completely randomized design using two factors including abiotic stress (drought and cold) and GB. Moreover, the principal component analysis based on the measured parameters manifested how the selected ROS scavengers were dispersed throughout the treatments. The results showed huge beneficial impacts of GB on the phenotypic traits of D. odorifera; GB also influences positively the antioxidant machinery, photosynthetic pigments, redox-homeostasis, and water status in D. odorifera seedlings under both stresses. Moreover, exogenous GB affects more the AOX pathway in D. odorifera under cold stress than under drought stress.
Failing to repair DNA double-strand breaks by either nonhomologous end joining (NHEJ) or homologous recombination (HR) poses a threat to genome integrity, and may have roles in the onset of aging and ...age-related diseases. Recent work indicates an age-related decrease of NHEJ efficiency in mouse models, but whether NHEJ and HR change with age in humans and the underlying mechanisms of such a change remain uncharacterized. Here, using 50 eyelid fibroblast cell lines isolated from healthy donors at the age of 16-75 years, we demonstrate that the efficiency and fidelity of NHEJ, and the efficiency of HR decline with age, leading to increased IR sensitivity in cells isolated from old donors. Mechanistic analysis suggests that decreased expression of XRCC4, Lig4 and Lig3 drives the observed, age-associated decline of NHEJ efficiency and fidelity. Restoration of XRCC4 and Lig4 significantly promotes the fidelity and efficiency of NHEJ in aged fibroblasts. In contrast, essential HR-related factors, such as Rad51, do not change in expression level with age, but Rad51 exhibits a slow kinetics of recruitment to DNA damage sites in aged fibroblasts. Further rescue experiments indicate that restoration of XRCC4 and Lig4 may suppress the onset of stress-induced premature cellular senescence, suggesting that improving NHEJ efficiency and fidelity by targeting the NHEJ pathway holds great potential to delay aging and mitigate aging-related pathologies.
Grey wolf optimizer (GWO) is a new meta-heuristic algorithm. The GWO algorithm mimics the leadership hierarchy and hunting mechanism of grey wolves in nature. Three main stages of hunting include: ...encircling, tracking and attacking. It is easy to fall into local optimum when used to optimize high-dimensional data, and there is imbalance between exploration and exploitation. An improved grey wolf optimizer based on tracking mode and seeking mode is proposed to improve the diversity of the population and the ability of the algorithm to balance exploration and exploitation. The algorithm is verified by simulation experiments in three parts. Firstly, the proposed grey wolf optimizer based on tracking mode (TGWO), the improved grey wolf optimizer based on seeking mode (SGWO), the improved grey wolf optimizer based on tracking and seeking mode (TSGWO), Grey Wolf Optimizer (GWO), Particle Swarm Optimization (PSO), Salp Swarm Algorithm (SSA), Sine Cosine Algorithm (SCA), Ant Lion Optimizer (ALO), Whale Optimization Algorithm (WOA) and Moth-flame Optimization (MFO) are adopted to optimize 21 typical benchmark functions respectively, and the obtained statistical simulation results are compared; Secondly, the improved algorithm proposed in this paper is compared with Binary Grey Wolf Optimizer (BGWO), Hybrid PSOGWO Optimization (PSOGWO) and GWO Algorithm Integrated with Cuckoo Search (GWOCS); Finally, it is applied to the lightest design engineering problem of pressure vessels. Simulation results show that the superior performance of the proposed algorithm for exploiting the optimum and it has advantages in terms of exploration. The improved grey wolf optimizer based on tracking mode and seeking mode can better solve function optimization and classical engineering problems with constraints. It was found the improved grey wolf optimizer based on tracking mode has the high precision and the characteristics of balanced exploration and exploitation.
Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination ...of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH. Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).
Objective
To evaluate the efficacy and safety of repeated low‐dose human recombinant erythropoietin (rhEPO) in the improvement of neurological outcomes in very preterm infants.
Methods
A total of 800 ...infants of ≤32‐week gestational age who had been in an intensive care unit within 72 hours after birth were included in the trial between January 2009 and June 2013. Preterm infants were randomly assigned to receive rhEPO (500IU/kg; n = 366) or placebo (n = 377) intravenously within 72 hours after birth and then once every other day for 2 weeks. The primary outcome was death or moderate to severe neurological disability assessed at 18 months of corrected age.
Results
Death and moderate/severe neurological disability occurred in 91 of 338 very preterm infants (26.9%) in the placebo group and in 43 of 330 very preterm infants (13.0%) in the rhEPO treatment group (relative risk RR = 0.40, 95% confidence interval CI = 0.27–0.59, p < 0.001) at 18 months of corrected age. The rate of moderate/severe neurological disability in the rhEPO group (22 of 309, 7.1%) was significantly lower compared to the placebo group (57 of 304, 18.8%; RR = 0.32, 95% CI = 0.19–0.55, p < 0.001), and no excess adverse events were observed.
Interpretation
Repeated low‐dose rhEPO treatment reduced the risk of long‐term neurological disability in very preterm infants with no obvious adverse effects. Ann Neurol 2016;80:24–34
•Both HAs and TFAs were detected in fried grass carp.•HAs concentrations was related to loss of water and fat content.•The types of TFAs of grass carp was consistent with that of the frying ...oil.•Linear relationship between the amount of 9t-18:1 in the refined soybean oil and No. of frying cycles was established.•The increasing of frying cycle times, provide the conditions for the formation of IQ, PhIP, MeIQx, and AαC.
The effects of frying temperature and the number of frying cycles on the formation of heterocyclic amines (HAs) and trans fatty acids (TFAs) in grass carp were investigated. 9t-18:1 FAs was detected in all samples. The TFA contents of samples fried at 150–210°C were not significantly different (P>0.05). The content and number of different types of HAs increased with increasing frying temperature. 9H-pyrido3,4-bindole (Norharman), 1-methyl-9H-pyrido 3,4-bindole (Harman), and 2-amino-3,7,8-trimethylimdazo4,5-fquinoxaline (7,8-diMeIQx) were detected in most of the tested samples. The differences in the surface colour (ΔE) increased with frying temperature, and ΔE of samples fried at 170°C was significantly higher than that of 150°C (P<0.05). The analysis of different cycle times revealed that the TFA levels increased with an increase in the usage period of the frying fat, and 9t,12t-18:2 FAs was detected after the 40th frying cycle. As the number of frying cycles increased, the number of different types of HAs increased, seven types of HAs were detected after the 25th frying cycle.
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