Search

Abstract Background Long non-coding RNAs (lncRNAs) have been extensively reported to play critical roles in the pathogenesis of various disease, especially in cancer. However, little is known about the role of lncRNAs in the pathogenesis of pediatric allergic asthma. Methods High-throughput sequencing analysis was performed to identify differentially expressed mRNAs and lncRNAs in peripheral blood mononuclear cells (PBMCs) from 3 children with allergic asthma and 3 matched healthy controls. Bioinformatics analysis was used to select candidate lncRNAs and mRNAs that may be involved in the pathogenesis of asthma. Candidate lncRNAs were validated in a larger size of asthma patients and healthy controls. Finally, lncRNAs and molecular pathways associated with the pathogenesis of allergic asthma were identified by competing endogenous RNA (ceRNA) analysis. Results Five differentially expressed lncRNAs were identified after high-throughput sequencing and verified by real-time PCR. LncRNAs ENST0000631797, TCONS_00004989 and ENST00000499459 were verified to be differentially expressed in allergic asthma. Besides, ENST00000499459/DIXDC1 axis was identified to play a crucial role in allergic asthma after comprehensive ceRNA network analysis. Conclusion ENST00000499459 and TCONS_00004989 are potential biomarkers for house dust mite-induced allergic asthma.

The pathophysiological mechanisms of the post-acute sequelae of COVID-19 (PASC) remain unclear. Sex differences not only exist in the disease severity of acute SARS-CoV-2 infection but also in the risk of suffering from PASC. Women have a higher risk of suffering from PASC and a longer time to resolution than men. To explore the possible immune mechanisms of PASC among non-elderly females, we mined single-cell transcriptome data from peripheral blood samples of non-elderly female patients with PASC and acute SARS-CoV-2 infection, together with age- and gender-matched non-PASC and healthy controls available from the Gene Expression Omnibus database. By comparing the differences, we found that a CD14+ monocyte subset characterized by higher expression of signal transducers and activators of transcription 2 (STAT2) (CD14+STAT2high) was notably increased in the PASC patients compared with the non-PASC individuals. The transcriptional factor (TF) activity analysis revealed that STAT2 and IRF9 were the key TFs determining the function of CD14+STAT2high monocytes. STAT2 and IRF9 are TFs exclusively involving type I and III interferon (IFN) signaling pathways, resulting in uncontrolled IFN-I signaling activation and type I interferonopathy. Furthermore, increased expression of common interferon-stimulated genes (ISGs) has also been identified in most monocyte subsets among the non-elderly female PASC patients, including IFI6, IFITM3, IFI44L, IFI44, EPSTI1, ISG15, and MX1. This study reveals a featured CD14+STAT2high monocyte associated with uncontrolled IFN-I signaling activation, which is indicative of a possible type I interferonopathy in the non-elderly female patients with PASC. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm. Through cell-to-cell contact or paracrine effects, they carry out biological tasks like immunomodulatory, anti-inflammatory, regeneration, and repair. Extracellular vesicles (EVs) are the primary mechanism for the paracrine regulation of MSCs. They deliver proteins, nucleic acids, lipids, and other active compounds to various tissues and organs, thus facilitating intercellular communication. Rheumatic diseases may be treated using MSCs and MSC-derived EVs (MSC-EVs) due to their immunomodulatory capabilities, according to mounting data. Since MSC-EVs have low immunogenicity, high stability, and similar biological effects as to MSCs themselves, they are advantageous over cell therapy for potential therapeutic applications in rheumatoid arthritis, systemic erythematosus lupus, systemic sclerosis, Sjogren's syndrome, and other rheumatoid diseases. This review integrates recent advances in the characteristics, functions, and potential molecular mechanisms of MSC-EVs in rheumatic diseases and provides a new understanding of the pathogenesis of rheumatic diseases and MSC-EV-based treatment strategies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense itchiness that is highly prevalent worldwide.The pathogenesis of AD is complex and closely related to genetic factors, immunopathogenic factors, environmental factors, and skin infections. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells derived from the mesenchymal stroma. They have anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous studies demonstrate that MSCs can play a therapeutic role in AD by regulating various immune cells, maintaining immune homeostasis, and promoting the repair of damaged tissues. The key mediators for their biological functions are extracellular vesicles (MSC-Evs) and soluble cytokines derived from MSCs. The safety and efficacy of MSCs have been demonstrated in clinical Phase I / IIa trials for AD. This paper provides a comprehensive review of the pathogenesis of AD and the currently published studies on the function of MSCs and MSC-Evs in AD, primarily including the pathogenesis and the immunomodulatory impacts of MSCs and MSC-Evs, along with advancements in clinical studies. It provides insights for comprehending AD pathogenesis and investigating treatments based on MSCs. [ABSTRACT FROM AUTHOR]

The recently discovered Cu46Zr33.5Hf13.5Al7 (at.%) bulk metallic glass (BMG) presents the highest glass-forming ability (GFA) among all known copper-based alloys, with a record-breaking critical casting thickness (or diameter) of 28.5 mm. At present, much remains to be explored about this new BMG that holds exceptional promise for engineering applications. Here, we report our study on the crystallization behavior of this new BMG, using isochronal and isothermal differential scanning calorimetry (DSC), X-ray diffraction (XRD), and transmission electron microscopy (TEM). With the calorimetric data, we determine the apparent activation energy of crystallization, the Avrami exponent, and the lower branch of the isothermal time–temperature–transformation (TTT) diagram. With XRD and TEM, we identify primary and secondary crystal phases utilizing samples crystallized to different degrees within the calorimeter. We also estimate the number density, nucleation rate, and growth rate of the primary crystals through TEM image analysis. Our results reveal that the crystallization in this BMG has a high activation energy of ≈360 kJ/mole and that the primary crystallization of this BMG produces a high number density (≈1021 m−3 at 475 °C) of slowly growing (growth rate < 0.5 nm/s at 475 °C) Cu10(Zr,Hf)7 nanocrystals dispersed in the glassy matrix, while the second crystallization event further produces a new phase, Cu(Zr,Hf)2. The results help us to understand the GFA and thermal stability of this new BMG and provide important guidance for its future engineering applications, including its usage as a precursor to glass–crystal composite or bulk nanocrystalline structures. [ABSTRACT FROM AUTHOR]

While most studies have considered diffusion in metallic glasses (MGs) to be normal, with a temporally asymptotic diffusivity at a given temperature (T), we report that the diffusion is anomalous and should be described as subdiffusion in pure Ta and pure V MGs—two examples chosen here because of chemical simplicity, fast relaxation, and minimal ambiguity. The diffusivity at a constant T (below the glass transition temperature) drops continuously with time t according to a negative power law instead of the commonly assumed exponential decay. To understand this, we trace the dynamic evolution of potential energy (Ep) and icosahedral short-range ordering (fico) of the system. We find that at large t, fico increases linearly with ln(t), causing Ep to decrease linearly with ln(t), with a remarkably simple linear correlation between fico and Ep. Based on Ep, we infer a continuously increasing effective migration energy barrier, also scaling linearly with ln(t), which perfectly recovers the negative power law time-dependence of diffusivity. The finding of anomalous diffusion and its origin in the fast-relaxing MGs calls out the need to distinguish potentially anomalous diffusion from normal diffusion in MGs, which is critical in disentangling time and temperature in experimental data and developing a robust theory for diffusion in MGs. The temporal scaling laws for diffusivity and structural and energy relaxations reported here may find their validity in other MGs and aid future theory development. In addition, we also discuss the effect of sample thermal history on the time-dependent diffusivity and how to prevent confusion caused by such effect. [ABSTRACT FROM AUTHOR]