Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Design, analysis, and simulation of a planar serial–parallel mechanism for a compliant robotic fish with variable stiffness

Biological evidence suggests that fish use muscles to stiffen their bodies and improve their swimming performance. Inspired by this phenomenon, we propose a planar serial–parallel mechanism with variable stiffness to mimic a swimming fish. Based on Lighthill’s elongated-body theory, we present a general method to design the body stiffness, which is related to morphological parameters and the swimming frequency. The results show that the stiffness profile is directly proportional to the square of the driving frequency. Furthermore, a SimMechanics model of a robotic fish is innovatively built. Numerical results show that the fish with the designed stiffness has the maximum speed when the driving frequency is close to the resonance frequency of fish body, and that the maximum speed is linearly proportional to the resonance frequency. The range of the Strouhal number given by simulations is also consistent with the range 0.25 < St < 0.35 required by the optimal efficiency. All these results agree well with biological observations, indicating that the swimming performance of fish is significantly affected by the body stiffness and the driving frequency

Sharp interface immersed boundary method for simulating three-dimensional swimming fish

A second order finite-difference numerical method is used to solve the Navier-Stokes equations of incompressible flow, in which the solid body with complex geometry is immersed into the fluid domain with orthogonal Cartesian meshes. To account for influences of the solid body, interactive forces are applied as boundary conditions at Cartesian grid nodes located in the exterior but in the immediate vicinity of the solid body. Fluid flow velocities in these nodes are reconstructed to track and control the deformation of the solid body, in which the local direction normal to the body surface is employed using the level-set function. The capabilities of this method are demonstrated by the application to fish swimming, and the computed behaviors of swimming fish agree well with experimental ones. The results elucidate that the ability of swimming fish to produce more thrust and high efficiency is closely related to the Reynolds number. The single reverse Karman street tends to appear when both the Strouhal number and tail-beating frequency are small, otherwise the double-row reverse Karman street appears. The algorithm can capture the geometry of a deformable solid body accurately, and performs well in simulating interactions between fluid flow and the deforming and moving body

Variable stiffness design of redundantly actuated planar rotational parallel mechanisms

Redundantly actuated planar rotational parallel mechanisms (RAPRPMs) adapt to the requirements of robots under different working conditions by changing the antagonistic internal force to tune their stiffness. The geometrical parameters of the mechanism impact the performances of modulating stiffness. Analytical expressions relating stiffness and geometrical parameters of the mechanism were formulated to obtain the necessary conditions of variable stiffness. A novel method of variable stiffness design was presented to optimize the geometrical parameters of the mechanism. The stiffness variation with the internal force was maximized. The dynamic change of stiffness with the dynamic location of the mechanism was minimized, and the robustness of stiffness during the motion of the mechanism was ensured. This new approach to variable stiffness design can enable off-line planning of the internal force to avoid the difficulties of on-line control of the internal force

CFD Studies of the Effects of Waveform on Swimming Performance of Carangiform Fish

Carangiform fish, like mackerel, saithe and bass, swim forward by rhythmically passing body waves from the head to the tail. In this paper, the undulating motions are decomposed into the travelling part and the standing part by complex orthogonal decomposition (COD), and the ratio between these two parts, i.e., the travelling index, is proposed to analyse the waveform of fish-like movements. To further study the relative influences of the waveform on swimming performance, a self-propelled model of carangiform fish is developed by the level set/immersed boundary (LS-IB) method, and the in-house code is tested by two cases of flow past a sphere and an oscillating cylinder, respectively. In this study, the travelling index is varied in ranges up to 50% larger or smaller than the biological data. The results show that carangiform fish seem to favour a fast and efficient swimming motion with a travelling index of around 0.6. Meanwhile, we study several numerical cases with different amplitude coefficients (0.5~1.1) and tail-beat frequency (2 Hz~5 Hz), and then compare their swimming performance with each other. We found that the forward speed is closely related to the travelling index and tail-beat frequency, while the swimming efficiency is increased with the tail-beat frequency and amplitude coefficient. These results are also consistent with biological observations, and they might provide beneficial guidance with respect to the future design of robotic fish

Causal relationship between gut microbiota and ankylosing spondylitis and potential mediating role of inflammatory cytokines: A mendelian randomization study.

Associations between gut microbiota and ankylosing spondylitis have been discovered in previous studies, but whether these associations reflect a causal relationship remains inconclusive. Aiming to reveal the bidirectional causal associations between gut microbiota and ankylosing spondylitis, we utilized publicly available genome wide association study summary data for 211 gut microbiota (GM) taxa and ankylosing spondylitis (AS) to conduct two sample mendelian randomization analyses. Mediation analysis was performed to explore mediating inflammatory cytokines. We found that genetically predicted higher abundance of Lactobacillaceae family, Rikenellaceae family and Howardella genus had suggestive associations with decreased risk of ankylosing spondylitis while genetic proxied higher abundance of Actinobacteria class and Ruminococcaceae_NK4A214_group genus was associated with increased risk of ankylosing spondylitis. IL23 and IFN-γ were potential mediating cytokines for GM dysbiosis, especially for Actinobacteria class, leading to AS. Our study provided a new exploration direction for the treatment of AS. Lactobacillaceae family, Rikenellaceae family, Howardella genus, Actinobacteria class and Ruminococcaceae_NK4A214_group genus are expected to become new therapeutic targets and monitoring indicators for AS

In Situ-Generated Heat-Resistant Hydrogen-Bonded Organic Framework for Remarkably Improving Both Flame Retardancy and Mechanical Properties of Epoxy Composites

In this study, the heat-resistant hydrogen-bonded organic framework (HOF) material HOF-FJU-1 was synthesized via in situ generation and then used as flame retardants (FRs) to improve the flame retardancy of epoxy resin (EP). HOF-FJU-1 can maintain high crystallinity at 450 °C and thus function as a flame retardant in EP. The study found that HOF-FJU-1 facilitates the improvement of char formation in EP, thus inhibiting heat transfer and smoke release during combustion. For EP/HOF-FJU-1 composites, the in situ-generated HOF-FJU-1 can remarkably improve both the mechanical properties and the flame retardancy of EP. Furthermore, the in situ-generated HOF-FJU-1 has better fire safety than the ex situ-generated HOF-FJU-1 at the same filling content. Thermal degradation products and flame retardation mechanisms in the gas and condensed phases were further investigated. This work demonstrates that the in situ-generated HOF-FJU-1 is promising to be an excellent flame-retardant candidate

Direct imaging of copper catalyst migration inside helical carbon nanofibers

By using a double-aberration-corrected (scanning) transmission electron microscope (STEM/TEM) at an acceleration voltage of only 80 kV, we demonstrate that, due to the low solubility of copper (Cu) in carbon and its affinity with oxygen (O), single-crystal Cu catalysts dissociate into small cuprous oxide (Cu2O) nanoparticles after the growth of carbon nanofibers, and Cu2O nanoparticles ultimately localize on the fiber surfaces. This new finding is a step toward a better understanding of the interactions between Cu catalysts and carbon nanomaterials and could suggest a simple and effective method for eliminating Cu impurities from the fibers

From Xiaoke to diabetes mellitus: a review of the research progress in traditional Chinese medicine for diabetes mellitus treatment

Abstract Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia resulting from insulin secretion defects or insulin resistance. The global incidence of DM has been gradually increasing due to improvements in living standards and changes in dietary habits, making it a major non-communicable disease that poses a significant threat to human health and life. The pathogenesis of DM remains incompletely understood till now, and current pharmacotherapeutic interventions are largely inadequate, resulting in relapses and severe adverse reactions. Although DM is not explicitly mentioned in traditional Chinese medicine (TCM) theory and clinical practice, it is often classified as “Xiaoke” due to similarities in etiology, pathogenesis, and symptoms. With its overall regulation, multiple targets, and personalized medication approach, TCM treatment can effectively alleviate the clinical manifestations of DM and prevent or treat its complications. Furthermore, TCM exhibits desirable therapeutic effects with minimal side effects and a favorable safety profile. This paper provides a comprehensive comparison and contrast of Xiaoke and DM by examining the involvement of TCM in their etiology, pathogenesis, treatment guidelines, and other relevant aspects based on classical literature and research reports. The current TCM experimental research on the treatment of DM by lowering blood glucose levels also be generalized. This innovative focus not only illuminates the role of TCM in DM treatment, but also underscores the potential of TCM in DM management