Intrinsic Surface Effects of Tantalum and Titanium on Integrin α5β1/ ERK1/2 Pathway-Mediated Osteogenic Differentiation in Rat Bone Mesenchymal Stromal Cells

Background/Aims: Accumulating evidence demonstrates the superior osteoinductivity of tantalum (Ta) to that of titanium (Ti); however, the mechanisms underlying these differences are unclear. Thus, the objective of the present study was to examine the effects of Ta and Ti surfaces on osteogenesis using rat bone mesenchymal stromal cells (rBMSCs) as a model. Methods: Ta and Ti substrates were polished to a mirror finish to minimize the influences of structural factors, and the intrinsic surface effects of the two materials on the integrin α5β1/mitogen-activated protein kinases 3 and 1 (ERK1/2) cascade-mediated osteogenesis of rBMSCs were evaluated. Alkaline phosphatase (ALP) activity, Alizarin Red staining, real-time polymerase chain reaction, and western blot assays of critical osteogenic markers were conducted to evaluate the effects of the two substrates on cell osteogenesis. Moreover, the role of the integrin α5β1/ERK1/2 pathway on the osteoinductive performance of Ta and Ti was assessed by up- and down-regulation of integrin α5 and β1 with RNA interference, as well as through ERK1/2 inhibition with U0126. Results: Osteogenesis of rBMSCs seeded on the Ta surface was superior to that of cells seeded on the Ti surface in terms of ALP activity, extracellular matrix calcification, and the expression of integrin α5, integrin β1, ERK1/2, Runt-related transcription factor 2, osteocalcin, collagen type I, and ALP at both the mRNA and protein levels. Moreover, down-regulation of integrin α5 or integrin β1, or ERK1/2 inhibition severely impaired the osteoblastic differentiation on the Ta surface. By contrast, over-expression of integrin α5 or integrin β1 improved osteogenesis on the Ti substrates, while subsequent ERK1/2 inhibition abrogated this effect. Conclusion: The integrin α5β1/ERK1/2 pathway plays a crucial role in regulating rBMSCs osteogenic differentiation; thus, the greater ability of a Ta surface to trigger integrin α5β1/ERK1/2 signaling may explain its better osteoinductivity. The different effects of Ta and Ti surfaces on rBMSC osteogenesis are considered to be related to the conductive behaviors between integrin α5β1 and the oxides spontaneously formed on the two metals. These results should facilitate the development of engineering strategies with Ta and Ti surfaces for improved osteogenesis in endosteal implants

Differential associations of cystatin C versus creatinine‐based kidney function with risks of cardiovascular event and mortality among South Asian individuals in the UK Biobank

Background: South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine‐ rather than cystatin C–based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results: Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine‐based estimated glomerular filtration rate categories (<45, 45–59, 60–89, and ≥90 mL/min per 1.73 m2) with risks of all‐cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55–3.65]) and incident HF (sub‐HR [sHR], 1.87 [95% CI, 1.09–3.22]) versus the eGFRcys ≥90 category; the creatinine‐based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine‐based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56–9.31]), incident HF (sHR, 4.96 [95% CI, 2.21–11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14–4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45–3.51]). Conclusions: Among South Asian individuals, cystatin C identified a high‐risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate–based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease

Cystatin C- and creatinine-based estimated GFR differences: prevalence and predictors in the UK Biobank

Rationale & objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study design: Cohort study. Setting & participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing

Optical Acceleration Measurement Method with Large Non-ambiguity Range and High Resolution via Synthetic Wavelength and Single Wavelength Superheterodyne Interferometry

Interferometric optomechanical accelerometers provide superior resolution, but the application is limited due to the non-ambiguity range that is always less than half of the wavelength, which corresponds to the order of mg. This paper proposes a novel acceleration measurement method based on synthetic wavelength and single wavelength superheterodyne interferometry to address this issue. Two acousto-optical modulators and several polarizers are introduced to the two-wavelength interferometry to create four beams with different frequencies and polarization states, and two ultra-narrow bandwidth filters are used to realize the single wavelength measurement simultaneously. This technique offers the possibility to expand the non-ambiguity range without compromising the high resolution. Also, the superheterodyne phase measurement and the corresponding processing algorithm are given to enable real-time measurement. A prototype is built and the preliminary experimental results are compared with the simulation results, showing good agreement. The results prove an estimated acceleration measurement resolution of around 10 μg and a non-ambiguity range of larger than 200 mg, which is more than 100 times that of the single wavelength-based optical accelerometer

An Untargeted Metabolomics Investigation of Milk from Dairy Cows with Clinical Mastitis by 1H-NMR

Mastitis is one of the diseases with the highest incidence in dairy cows, causing huge economic losses to the dairy industry all over the world. The aim of the study was to characterize mastitic milk metabolome through untargeted nuclear magnetic resonance spectroscopy (1H-NMR). Taking advantage of the high reproducibility of 1H-NMR, we had the opportunity to provide quantitative information for all the metabolites identified. Fifty-four molecules were characterized, sorted mainly into the chemical groups, namely amino acids, peptides and analogues, carbohydrates and derivates, organic acids and derivates, nucleosides, nucleotides and analogues. Combined with serum metabolomic investigations, several pathways were addressed to explain the mechanisms of milk metabolome variation affected by clinical mastitis, such as tricarboxylic acid cycle (TCA cycle) and phenylalanine, tyrosine and tryptophan biosynthesis. These results provide a further understanding of milk metabolome altered by clinical mastitis, which can be used as a reference for the further milk metabolome investigations

Single Chip-Based Nano-Optomechanical Accelerometer Based on Subwavelength Grating Pair and Rotated Serpentine Springs

Optical coupling between subwavelength grating pairs allows for the precise measurement of lateral or vertical displacement of grating elements and gives rise to different types of displacement and inertial sensors. In this paper, we demonstrate a design for a nano-optomechanical accelerometer based on a subwavelength grating pair that can be easily fabricated by a single Silicon-on-insulator (SOI) chip. The parameters of the subwavelength grating pair-based optical readout, including period, duty cycle, thickness of grating and metal film, and the distance of the air gap, were optimized by combining a genetic algorithm and rigorous coupled wavelength analysis (RCWA) to obtain the optimal sensitivity to the displacement of suspended grating element and the acceleration. A corresponding mechanical design was also completed to meet the highly sensitive acceleration measurement requirement while considering the mechanical cross-axis sensitivity, dynamic range, bandwidth, and fabrication feasibility. This device was verified by both RCWA and finite-different-time-domain methods, and a tolerance analysis was also completed to confirm that it is able to achieve the extremely high optical displacement sensitivity of 1.8%/nm, acceleration-displacement sensitivity of 1.56 nm/mg, and acceleration measurement sensitivity of more than 2.5%/mg, which is almost one order of magnitude higher than any reported counterparts. This work enables a single SOI-based high performance accelerometer, and provides a theoretical basis and fabrication guides for the design

Visible–Infrared Person Re-Identification via Global Feature Constraints Led by Local Features

Smart security is needed for complex scenarios such as all-weather and multi-scene environments, and visible–infrared person re-identification (VI Re-ID) has become a key technique in this field. VI Re-ID is usually modeled as a pattern recognition issue, which faces the problems of inter-modality and intra-modality discrepancies. To alleviate these problems, we designed the Local Features Leading Global Features Network (LoLeG-Net), a representation learning network. Specifically, for cross-modality discrepancies, we employed a combination of ResNet50 and non-local attention blocks to obtain the modality-shareable features and convert the problem to a single-modality person re-identification (Re-ID) problem. For intra-modality variations, we designed global feature constraints led by local features. In this method, the identity loss and hetero-center loss were employed to alleviate intra-modality variations of local features. Additionally, hard sample mining triplet loss combined with identity loss was used, ensuring the effectiveness of global features. With this method, the final extracted global features were much more robust against the background environment, pose differences, occlusion and other noise. The experiments demonstrate that LoLeG-Net is superior to existing works. The result for SYSU-MM01 was Rank-1/mAP 51.40%/51.41%, and the result for RegDB was Rank-1/mAP 76.58%/73.36%

Visible–Infrared Person Re-Identification via Global Feature Constraints Led by Local Features

Smart security is needed for complex scenarios such as all-weather and multi-scene environments, and visible–infrared person re-identification (VI Re-ID) has become a key technique in this field. VI Re-ID is usually modeled as a pattern recognition issue, which faces the problems of inter-modality and intra-modality discrepancies. To alleviate these problems, we designed the Local Features Leading Global Features Network (LoLeG-Net), a representation learning network. Specifically, for cross-modality discrepancies, we employed a combination of ResNet50 and non-local attention blocks to obtain the modality-shareable features and convert the problem to a single-modality person re-identification (Re-ID) problem. For intra-modality variations, we designed global feature constraints led by local features. In this method, the identity loss and hetero-center loss were employed to alleviate intra-modality variations of local features. Additionally, hard sample mining triplet loss combined with identity loss was used, ensuring the effectiveness of global features. With this method, the final extracted global features were much more robust against the background environment, pose differences, occlusion and other noise. The experiments demonstrate that LoLeG-Net is superior to existing works. The result for SYSU-MM01 was Rank-1/mAP 51.40%/51.41%, and the result for RegDB was Rank-1/mAP 76.58%/73.36%