Fibrosis usually results from dysregulated wound repair and is characterized by excessive scar tissue. It is a complex process with unclear mechanisms. Accumulating evidence indicates that epigenetic ...alterations, including histone acetylation, play a pivotal role in this process. Histone acetylation is governed by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are enzymes that remove the acetyl groups from both histone and nonhistone proteins. Aberrant HDAC activities are observed in fibrotic diseases, including cardiac and pulmonary fibrosis. HDAC inhibitors (HDACIs) are molecules that block HDAC functions. HDACIs have been studied extensively in a variety of tumors. Currently, there are four HDACIs approved by the US Food and Drug Administration for cancer treatment yet none for fibrotic diseases. Emerging evidence from in vitro and in vivo preclinical studies has presented beneficial effects of HDACIs in preventing or reversing fibrogenesis. In this review, we summarize the latest findings of the roles of HDACs in the pathogenesis of cardiac and pulmonary fibrosis and highlight the potential applications of HDACIs in these two fibrotic diseases.
In this article, a Fast Linear Elastic Eigenvalue Problem Solver (FLEEPS) is developed to calculate the band structures of three-dimensional (3D) isotropic phononic crystals (PnCs). In brief, FLEEPS ...solves in linear time complexity the smallest few eigenvalues and associated eigenvectors of the linear elastic eigenvalue problem originating from the finite difference discretization of the frequency-domain linear elastic wave equation. Notably, FLEEPS employs the weighted singular value decomposition based preconditioner to greatly improve the convergence rate of the conjugate gradient iteration, and uses the fast Fourier transform algorithm to accelerate this preconditioner times a vector, based on the structured decomposition of the dense unitary factor
T
of this preconditioner. Band structure calculations of several 3D isotropic PnCs are presented to showcase the capabilities of FLEEPS. The preliminary MATLAB implementation of FLEEPS is available at
https://github.com/FAME-GPU/FLEEPS-MATLAB
.
Background： Nowadays, social media tools such as short message service, Twitter, video, and web-based systems are more and more used in clinical follow-up, making clinical follow-up much more time- ...and cost-effective than ever before. However, as the most popular social media in China, little is known about the utility of smartphone WeChat application in follow-up. In this study, we aimed to investigate the feasibility and superiority of WeChat application in clinical follow-up. Methods： A total of 108 patients diagnosed with head and neck tumor were randomized to WeChat follow-up （WFU） group or telephone follow-up （TFU） group for 6-month follow-up. The follow-ups were delivered by WeChat or telephone at 2 weeks, 1, 2, 3, and 6 months to the patients after being discharged. The study measurements were time consumption for follow-up delivery, total economic cost, lost-to-follow-up rate, and overall satisfaction for the follow-up method. Results： Time consumption in WFU group for each patient （23.36 ± 6.16 min） was significantly shorter than that in TFU group （42.89 ± 7.15 min） （P 〈 0.001 ）; total economic cost in WFU group （RMB 90 Yuan） was much lower than that in TFU group （RMB 196 Yuan）. Lost-to-follow-up rate in the WFU group was 7.02% （4/57） compared with TFU group, 9.80% （5/51 ）, while no significance was observed （95% confidence interval CI： 0.176-2.740; P = 0.732）. The overall satisfaction rate in WFU group was 94.34% （50/53） compared with 80.43% （37/46） in TFU group （95% CI： 0.057-0.067; P = 0.034）. Conclusions： The smartphone WeChat application was found to be a viable option for follow-up in discharged patients with head and neck tumors. WFU was time-effective, cost-effective, and convenient in communication. This doctor-led follow-up model has the potential to establish a good physician-patient relationship by enhancing dynamic communications and providing individual health instructions.
As a set of inflammatory disorders, spondyloarthritis (SpA) exhibits distinct pathophysiological, clinical, radiological, and genetic characteristics. Due to the extra-articular features of this ...disorder, early recognition is crucial to limiting disability and improving outcomes. Gut dysbiosis has been linked to SpA development as evidence grows. A pathogenic SpA process is likely to occur when a mucosal immune system interacts with abnormal local microbiota, with subsequent joint involvement. It is largely unknown, however, how microbiota alterations predate the onset of SpA within the “gut-joint axis”. New microbiome therapies, such as probiotics, are used as an adjuvant therapy in the treatment of SpA, suggesting that the modulation of intestinal microbiota and/or intestinal barrier function may contribute to the prevention of SpA. In this review, we highlight the mechanisms of SpA by which the gut microbiota impacts gut inflammation and triggers the activation of immune responses. Additionally, we analyze the regulatory role of therapeutic SpA medication in the gut microbiota and the potential application of probiotics as adjunctive therapy for SpA.
Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease with limited therapeutic options. Aspirin can alleviate liver, kidney, and cardiac fibrosis. However, its role in lung ...fibrosis is unclear. This study aims to investigate the effects of aspirin on lung fibroblast differentiation and pulmonary fibrosis. TGF-β1-induced human embryonic lung fibroblasts, IPF lung fibroblasts, and bleomycin-induced lung fibrosis mouse model were used in this study. The results showed that aspirin significantly decreased the expression of Collagen 1A1, Fibronectin, Alpha-smooth muscle actin, and equestosome1, and increased the ratio of light chain 3 beta II/I and the number of autophagosome in vivo and in vitro; reduced bleomycin-induced lung fibrosis. Aspirin also decreased the ratios of phosphorylated phosphatidylinositol 3 kinase (p-PI3K)/PI3K, protein kinase B (p-AKT)/AKT, and mechanistic target of rapamycin (p-mTOR)/mTOR in vitro. Autophagy inhibitor 3-methyladenine, bafilomycin-A1, and AKT activator SC-79 abrogated the effects of aspirin. These findings indicate that aspirin ameliorates pulmonary fibrosis through a PI3K/AKT/mTOR-dependent autophagy pathway.
•Aspirin inhibits pulmonary fibrosis in lung fibroblasts and mice.•Aspirin induces autophagy.•Aspirin may block fibroblasts differentiation by inducing autophagy.•Aspirin induces autophagy by inhibiting PI3K/AKT/mTOR pathway.•Aspirin ameliorates pulmonary fibrosis through a PI3K/AKT/mTOR-dependent autophagy pathway.
In this paper, we present a unified finite difference framework to efficiently compute band structures of three dimensional linear non-dispersive isotropic photonic crystals with any of 14 Bravais ...lattice structures to a reasonable accuracy. Specifically, we redefine a suitable orthogonal coordinate system, and meticulously reformulate the Bloch condition for oblique Bravais lattices, and clearly identify the hierarchical companion matrix structure of the resulting discretized partial derivative operators. As a result, eigen-decompositions of discretized partial derivative operators and notably the discretized double-curl operator of any size, become trivial, and more importantly, the nullspace free method for the Maxwell’s equations holds naturally in all 14 Bravais lattices. Thus, the great difficulty arising from high multiplicity of zero eigenvalues has been completely overcome. On the basis of these results, we perform calculations of band structures of several typical photonic crystals to demonstrate the efficiency and accuracy of our algorithm.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with unknown cause and limited treatment options. Its mechanism needs to be further explored. Sirtuin2 (Sirt2), a nicotinamide adenine ...dinucleotide (NAD)-dependent deacetylase, has been proved to be involved in the fibrosis and inflammation in the liver, kidney and heart. In this study, we aimed to evaluate the role of Sirt2 in pulmonary fibrosis. We found that Sirt2 expression was upregulated in transforming growth factor-
1 (TGF-
1) treated human embryonic lung fibroblasts. Sirt2 inhibitor AGK2 or the knockdown of Sirt2 expression by targeting small interfering RNA (siRNA) suppressed the fibrogenic gene
-SMA and Fibronectin expression in TGF-
1 treated fibroblasts and primary lung fibroblasts derived from patients with IPF. In addition, Sirt2 inhibition suppresses the phosphorylation of Smad2/3. Co-immunoprecipitation (Co-IP) showed that there is interaction between Sirt2 and Smad3 in the TGF-
1 treated lung fibroblasts. In bleomycin-induced pulmonary fibrosis in mice, AGK2 treatment significantly mitigated the degree of fibrosis and decreased the phosphorylation of Smad2/3. These data suggest that Sirt2 may participate in the development of IPF
regulating the Smad2/3 pathway. Inhibition of Sirt2 would provide a novel therapeutic strategy for this disease.
This paper focuses on studying the eigenstructure of generalized eigenvalue problems (GEPs) arising in the three-dimensional source-free Maxwell equations for bi-anisotropic complex media with a ...3-by-3 permittivity tensor ε>0, a permeability tensor μ>0, and scalar magnetoelectric coupling constants ξ=ζ̄=ıγ. The bi-Lebedev scheme is appealing because it preserves the symmetry inherent to the Maxwell eigenvalue problem exactly and because full degrees of freedom of electromagnetic fields at each grid point are taken into account in the discretization. The resulting GEP has eigenvalues appearing in quadruples {±ω,±ω̄}. We consider two main scenarios, where γ<γ∗ and γ>γ∗ with γ∗ as a critical value. In the former case, all the eigenvalues are real. In the latter case, the GEP has complex eigenvalues, and we particularly focus on the bifurcation of the eigenstructure of the GEPs. Numerical results demonstrate that the newborn ground state has occurred after γ=γ̃>γ∗, and the associated eigenvector has an exotic phenomenon of localization. Moreover, the Poynting vectors of the newborn eigenvector not only are concentrated in the material but also display exciting patterns.
In this article, we propose the Fast Algorithms for Maxwell’s Equations (FAME) package for solving Maxwell’s equations for modeling three-dimensional photonic crystals. FAME combines the null-space ...free method with fast Fourier transform (FFT)-based matrix-vector multiplications to solve the generalized eigenvalue problems (GEPs) arising from Yee’s discretization. The GEPs are transformed into a null-space free standard eigenvalue problem with a Hermitian positive-definite coefficient matrix. The computation times for FFT-based matrix-vector multiplications with matrices of dimension 7 million are only 0.33 and 3.6 × 10
− 3
seconds using MATLAB with an Intel Xeon CPU and CUDA C++ programming with a single NVIDIA Tesla P100 GPU, respectively. Such multiplications significantly reduce the computational costs of the conjugate gradient method for solving linear systems. We successfully use FAME on a single P100 GPU to solve a set of GEPs with matrices of dimension more than 19 million, in 127 to 191 seconds per problem. These results demonstrate the potential of our proposed package to enable large-scale numerical simulations for novel physical discoveries and engineering applications of photonic crystals.
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