Background Osteoarthritis (OA) is a worldwide public health concern, mainly afflicting older adults. Although the etiology of OA remains unclear, environmental factors are increasingly considered as ...non-negligible risk factors. This study aims to evaluate the associations of urinary metals with OA risk and the mediated effect of biological aging. Methods Nine urinary metal concentrations were detected among 12,584 U.S. adults based on the National Health and Nutrition Examination Survey (NHANES), including barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), antimony (Sb), thallium (Tl), and uranium (Tu). Multivariable logistic regression and weighted quantile sum (WQS) regression were used to explore the associations of single metal and mixed metals with OA risk, respectively. Furthermore, biological aging was measured from different perspectives, including cell senescence (telomere length) and whole-body aging (phenotypic age and biological age). Mediation analyses were conducted to investigate the mediated effects of aging on the associations of metals with OA risk. Results In the single-exposure model, Cd, Co, and Cs were identified to be positively associated with OA risk, with odds ratios (OR) ranging from 1.48 to 1.64 (all P < 0.05). Mixed-exposure analyses showed consistent associations (OR 1.23, 95%CI 1.10 to 1.37) and highlighted that Cd, Co, and Cs were responsible for the outcomes. Additionally, Cd, Co, Cs, Pb, and Tl were positively associated with biological aging markers, while all biological aging markers had significant associations with OA risk. Further mediation analyses showed that the associations of single metal (mainly Cd and Cs) and mixed metals with OA risk parallelly mediated by the above biological aging markers, with the proportion of mediation ranging from 16.89 to 69.39% (all P < 0.05). Moreover, such associations were also serially mediated through telomere length-biological age path and telomere length-phenotypic age path (the proportion of mediation: 4.17-11.67%), indicating that metals accelerated cell senescence to lead to whole-body aging and finally aggravated OA progress. Conclusions These findings suggested that exposure to metals increased OA risk, which was possibly and partly mediated by biological aging. Keywords: Heavy metals, Osteoarthritis, Joint exposure, Biological aging, Mediation
Transcription Dynamics in Living Cells Lenstra, Tineke L; Rodriguez, Joseph; Chen, Huimin ...
Annual review of biophysics,
07/2016, Volume:
45
Journal Article
Peer reviewed
Open access
The transcription cycle can be roughly divided into three stages: initiation, elongation, and termination. Understanding the molecular events that regulate all these stages requires a dynamic view of ...the underlying processes. The development of techniques to visualize and quantify transcription in single living cells has been essential in revealing the transcription kinetics. They have revealed that (a) transcription is heterogeneous between cells and (b) transcription can be discontinuous within a cell. In this review, we discuss the progress in our quantitative understanding of transcription dynamics in living cells, focusing on all parts of the transcription cycle. We present the techniques allowing for single-cell transcription measurements, review evidence from different organisms, and discuss how these experiments have broadened our mechanistic understanding of transcription regulation.
•Numerical results departure from the growth direction selection law (DGP law) for higher pulling velocities.•The dependence of the coefficients f and g in the DGP law on μ (μ = Vp/Vc) for a fixed ...misorientation angle is discussed.•The dendritic tip shapes of tilted and non-tilted dendrites were compared.•The reason why our numerical results departure from the DGP law is discussed.
In this paper, the growth direction selection of tilted dendritic arrays in directional solidification over a wide range of pulling velocity was investigated by using a thin-interface phase-field model. A systematic convergence study with respect to the interface width for various pulling velocities was first carried out to keep simulated results that are independent of interface width. In our simulations, all data points effectively collapse to the DGP (Deschamps, Georgelin, and Pocheau) law (Phys Rev E 78 (2008) 011605-1-13) for lower pulling velocities while numerical results departure from the DGP law for higher pulling velocity. Based on the data from phase-field simulations, we discussed the dependence of the coefficients f and g in DGP law on μ (μ = Vp/Vc) for a fixed misorientation angle. The dendritic tip shapes of tilted and non-tilted dendrites were compared, and the evolution of tip radius with the variation of Vp was studied. Then, we discuss the reason why our numerical results departure from the DGP law for larger pulling velocities based on the variation of dendritic tip radius with the increase of the pulling velocity for a given Péclet number.
This study examines whether auditors incorporate their clients’ corporate culture into audit pricing. We construct a measure of corporate collaboration culture using textual analysis of public firms’ ...10‐K reports. We find that firms with more collaboration culture pay lower audit fees. We argue that firms with a culture of collaboration emphasize harmony among people, leading to lower litigation risk, which lowers auditor risk premiums. Collaboration culture also encourages employees’ reporting of errors and problems, leading to lower control risk, which lowers audit risk premiums. Using path analysis and a structural equation model, our findings support the argument. Moreover, we do not find evidence supporting alternative explanations of reduced audit quality and significant auditor changes. The negative relation between collaboration culture and audit fees is robust to multiple alternative measures of collaboration culture, but we caution about the interpretation of the economic significance of our finding.
Oral diseases, such as periapical periodontitis and periodontitis, are characterized by inflammation-induced bone loss. LL-37, a human antimicrobial peptide (AMP), has multiple biological functions ...and the potential to promote osteogenesis. Therefore, this study aimed to investigate the regulatory effects of LL-37 within normal and inflammatory microenvironments. The roles of P2X7 receptor (P2X7R) and mitogen-activated protein kinase (MAPK) signaling pathway were also demonstrated. The results showed that LL-37 promoted bone marrow stromal cell (BMSC) proliferation, migration and osteogenic differentiation. LL-37 inhibited the expression of the inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) at both protein and gene levels, and attenuated the lipopolysaccharide (LPS)-induced inhibition of osteogenesis. Immunofluorescence (IF) confirmed P2X7R expression in BMSCs. BBG, a P2X7R antagonist, significantly attenuated LL-37-promoted osteogenesis. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK) increased after LL-37 stimulation, which did not affect p38 phosphorylation. The effects of LL-37 on osteogenesis-related gene expression were markedly attenuated by selective inhibitors of ERK1/2 and JNK. Furthermore, a mouse model of LPS-stimulated calvarial osteolysis was established, and results showed that LL-37 markedly inhibited osteoclastic bone resorption. In conclusion, we speculate that LL-37 inhibits inflammation and promotes BMSC osteogenesis via P2X7R and MAPK signaling pathway.
Modern cellular biology faces several major obstacles, such as the determination of the concentration of active sites corresponding to chemical substances. In recent years, the popular small-molecule ...fluorescent probes have completely changed the understanding of cellular biology through their high sensitivity toward specific substances in various organisms. Mitochondria and lysosomes are significant organelles in various organisms, and their interaction is closely related to the development of various diseases. The investigation of their structure and function has gathered tremendous attention from biologists. The advanced nanoscopic technologies have replaced the diffraction-limited conventional imaging techniques and have been developed to explore the unknown aspects of mitochondria and lysosomes with a sub-diffraction resolution. Recent progress in this field has yielded several excellent mitochondria- and lysosome-targeted fluorescent probes, some of which have demonstrated significant biological applications. Herein, we review studies that have been carried out to date and suggest future research directions that will harness the considerable potential of mitochondria- and lysosome-targeted fluorescent probes.
In this study, hollow mesoporous silica (HMSN) was created to facilitate drug distribution using the hard template method. The oxidized hyaluronic acid (oxiHA) was coated on the carrier surface by ...the Schiff base reaction, producing the pH-responsive nanoparticles HMSNs-DOX-oxiHA targeted by CD44 and preventing drug leakage from mesopores. The prepared nanoparticles had a size of 151.79 ± 13.52 nm and a surface potential of −8.42 ± 0.48 mV. The rich mesoporous structure and internal cavity of HMSNs-NH2 achieved the effective encapsulation and loading rates of doxorubicin (DOX) at 76.84 ± 0.24 % and 18.73 ± 0.05 %, respectively. Owing to the pH sensitivity of imine bonds, HMSNs-DOX-oxiHA has a good pH response and release performance. The in vitro experiments showed that the nanoparticles were not cytotoxic and could enhance HCT-116 uptake efficiency by hyaluronic acid/CD44 receptor-mediated endocytosis, effectively inhibiting tumor cell proliferation and reducing toxic side effects on normal cells. In summary, the polysaccharide-based nano-drug delivery system constructed in this experiment not only has the basic response properties of a carrier but also introduces the bioactive advantages of natural polysaccharides.
Pleural effusion (PE) is a common clinical feature that presents a diagnostic challenge for clinicians. In this retrospective study, we aimed to assess the biomarkers, ratios, and multiple indicators ...in serum and Pleural effusion for the differential diagnosis of tuberculous pleural effusion (TPE) from non-tuberculosis effusion (non-TPE). The participants, who were divided into two groups: TPE and non-TPE (MPE and PPE), from Ningbo First Hospital, were incorporated in this study. The clinical and laboratory features were collected and analyzed using logistic regression analysis. Twelve biomarkers and their ratios in serum and PE were investigated for TPE versus non-TPE. Additionally, the value of multiple indicators for joint diagnosis was estimated. Biomarkers and ratios showed good diagnostic performance. The five variables including Serum ADA, IGRA, Effusion ADA, Effusion ADA/Serum ADA and Effusion LDH/Effusion ADA were identified as valuable parameters for differential diagnosis of TPE from non-TPE. The combined diagnosis of the five indexes yielded the highest diagnostic accuracy for TPE with an AUC (0.919), sensitivity (90.30%), and specificity (94.50%). The biomarkers and ratios demonstrated strong diagnostic performance, and the utilization of multiple indicators for joint diagnosis can improve the diagnostic efficacy of tuberculous pleurisy.
Infections caused by antibiotic-resistant bacteria are a major public health threat. The emergence and spread of antibiotic resistance genes (ARGs) in the environment or clinical setting pose a ...serious threat to human and animal health worldwide. Horizontal gene transfer (HGT) of ARGs is one of the main reasons for the dissemination of antibiotic resistance in vitro and in vivo environments. There is a consensus on the role of mobile genetic elements (MGEs) in the spread of bacterial resistance. Most drug resistance genes are located on plasmids, and the spread of drug resistance genes among microorganisms through plasmid-mediated conjugation transfer is the most common and effective way for the spread of multidrug resistance. Experimental studies of the processes driving the spread of antibiotic resistance have focused on simple in vitro model systems, but the current in vitro protocols might not correctly reflect the HGT of antibiotic resistance genes in realistic conditions. This calls for better models of how resistance genes transfer and disseminate in vivo. The in vivo model can better mimic the situation that occurs in patients, helping study the situation in more detail. This is crucial to develop innovative strategies to curtail the spread of antibiotic resistance genes in the future. This review aims to give an overview of the mechanisms of the spread of antibiotic resistance genes and then demonstrate the spread of antibiotic resistance genes in the in vivo model. Finally, we discuss the challenges in controlling the spread of antibiotic resistance genes and their potential solutions.
In land battlefield environments, aerosol particles can cause laser beams to undergo attenuation, thus deteriorating the operational performance of military laser devices. The particle size ...distribution (PSD) and extinction coefficient are key optical properties for assessing the attenuation characteristics of laser beams caused by aerosol particles. In this study, we employed the laser diffraction method to measure the PSDs of graphite smoke screen, copper powder smoke screen, iron powder smoke screen, ground dust, and soil explosion dust. We evaluated the goodness of fit of six common unimodal PSD functions and a bimodal lognormal PSD function employed for fitting these aerosol particles using the root mean square error (RMSE) and adjusted R2, and selected the optimal PSD function to evaluate their extinction coefficients in the laser wavelength range of 0.249~12 μm. The results showed that smoke screens, ground dust, and soil explosion dust exhibited particle size ranges of 0.7~50 µm, 1~400 µm, and 1.7~800 μm, respectively. The lognormal distribution had the best goodness of fit for fitting the PSDs of these aerosol particles in the six unimodal PSD functions, followed by the gamma and Rosin–Rammler distributions. For the bimodal aerosol particles with a lower span, the bimodal lognormal PSD functions exhibited the best goodness of fit. The graphite smoke screen exhibited the highest extinction coefficient, followed by the copper and iron powder smoke screens. In contrast, the ground dust and soil explosion dust exhibited the lowest extinction coefficients, reaching their minimum values at a wavelength of approximately 8.2 μm. This study provides a basis for analyzing and improving the detection and recognition performance of lasers in land battlefield environments.
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