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Methyltransferase-like 3 (METTL3), an RNA N6-methyladenosine (m6A) methyltransferase, is essential for the m6A mRNA modification. As a key enzyme of m6A methylation modification, METTL3 has been implicated in immune and inflammation regulation. However, little is known of the role and underlying mechanism of METTL3 in rheumatoid arthritis (RA). The aim of the present study is to elucidate the function and potential mechanism of METTL3 in RA pathogenesis. We used quantitative real-time polymerase chain reaction to detect the expression of METTL3 in RA patients and controls as well as the macrophage cell line. CCK-8 was used for cell proliferation assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to estimate the generation of IL-6 and TNF-α in macrophages. Western blot and immunofluorescence were applied to evaluate the activation of NF-κB in macrophages. The expression of METTL3 was significantly elevated in patients with RA. It was positively associated with CRP and ESR, two common markers for RA disease activity. Besides, LPS could enhance the expression and biological activity of METTL3 in macrophages, while overexpression of METTL3 significantly attenuated the inflammatory response induced by LPS in macrophages. Moreover, the effect of METTL3 on LPS-induced inflammation in macrophages was dependent on NF-κB. This study firstly demonstrates the critical role of METTL3 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA.

Rheumatoid arthritis is a common systemic and autoimmune disease characterized by symmetrical and inflammatory destruction of distal joints. Its primary pathological characters are synovitis and vasculitis. Accumulating studies have implicated the critical role of non-coding RNAs (ncRNAs) in inflammation and autoimmune regulation, primarily including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). NcRNAs are significant regulators in distinct physiological and pathophysiological processes. Many validated non-coding RNAs have been identified as promising biomarkers for the diagnosis and treatment of RA. This review will shed some light on RA pathogenesis and be helpful for identifying potential ncRNA biomarkers for RA.

Accumulating studies have indicated that the gut microbiota plays a pivotal role in the onset of autoimmune diseases by engaging in complex interactions with the host. This review aims to provide a comprehensive overview of the existing literatures concerning the relationship between the gut microbiota and autoimmune diseases, shedding light on the complex interplay between the gut microbiota, the host and the immune system. Furthermore, we aim to summarize the impacts and potential mechanisms that underlie the interactions between the gut microbiota and the host in autoimmune diseases, primarily focusing on systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, type 1 diabetes mellitus, ulcerative colitis and psoriasis. The present review will emphasize the clinical significance and potential applications of interventions based on the gut microbiota as innovative adjunctive therapies for autoimmune diseases.

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.

A multi-functional nine-channel full-spectrum light emitting diode color temperature palette is proposed. The color temperature (CCT) of the palette can be continuously tuned at 1K interval within the range of 2500K—6500K. A high color rendering index (CRI) is achieved, with Ra > 94 and R1—R15 > 90. A fidelity index (Rf) greater than 91 is obtained, and the gamut index (Rg) within the range of 96 ≤ Rg ≤ 104 is achieved. Additionally, A chromaticity deviation (Duv) within the range of |Duv| < 0.001 is realized. The circadian effect with melanopic efficacy of luminous radiation(MELR) of 0.6 mW/lm—1.14 mW/lm and circadian action factor(CAF) of 0.289 blm/lm—0.656 blm/lm are obtained. To verify the theoretical model’s stability, the Gaussian distribution function of monochromatic LED spectrum is adjusted to induce a 5% asymmetry in integral areas, and the FWHM is offset by ±10%, simulating the non-ideal conditions in practical applications to assess the model’s robustness. The color temperature palette enables precise control and reproduction of CCT of sunlight with corresponding circadian effect, which is of positive significance for visual fields such as photography or art exhibitions and regulation of circadian rhythm.

Accumulating studies have suggested that long non-coding RNAs (lncRNAs) have drawn more and more attention in rheumatoid arthritis (RA), which can function as competitive endogenous RNAs (ceRNAs) in inflammation and immune disorders. Previously, we have found that lncRNA HIX003209 is differentially expressed in RA. However, the precise mechanism of lncRNA HIX003209 in RA is still vague. We aim to elucidate the role and its targeted microRNA of lncRNA HIX003209 in RA as ceRNA. Significantly increased expression of lncRNA HIX003209 was observed in the peripheral blood mononuclear cells (PBMCs) from RA cases. It was positively associated with TLR2 and TLR4 in RA. Besides, peptidoglycan (PGN) and lipopolysaccharide (LPS) could enhance the expression of lncRNA HIX003209, which reversely promoted the proliferation and activation of macrophages through IκBα/NF-κB signaling pathway. Moreover, HIX003209 was involved in TLR4-mediated inflammation via targeting miR-6089 in macrophages. LncRNA HIX003209 functions as a ceRNA and exaggerates inflammation by sponging miR-6089 through TLR4/NF-κB pathway in macrophages, which offers promising therapeutic strategies for RA.

Background Little is known regarding both the role of myeloperoxidase (MPO) and the impact of mesenchymal stem cells (MSCs) on inflammatory and immune responses in ankylosing spondylitis (AS). This study is aimed to explore the role of MPO and the regulatory effect of umbilical cord-derived MSCs on MPO expression in monocytes in AS. Methods MPO mRNA expression in the peripheral blood mononuclear cells (PBMCs) was detected by Real-time PCR. Cytokines including IL-2, IFN-γ, IL-17 A, IL-4, IL-10, IL-6 and TNF-α were determined by flow cytometry. A co-culture system was established by culturing THP-1 cells with MSCs at a ratio of 5:1. Results Increased mRNA expression of MPO was observed in PBMCs of AS patients compared to healthy controls ( P  < 0.05). The mRNA expression of MPO was positively associated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) ( P  < 0.05) in AS. Besides, the levels of IL-2, IL-10, IFN-γ, IL-17 A, IL-4, IL-6, TNF-α in plasma were notably increased in AS ( P  < 0.05). Positive correlations between MPO expression and IL-2, IFN -γ, IL-4, TNF-α as well as IL-6 were demonstrated in AS ( P  < 0.05). Furthermore, MSCs remarkably suppressed the mRNA expression of MPO along with the secretion of IL-17 A and TNF-α, but promoted IL-10 generation in monocytes. Conclusion MPO expression is significantly upregulated and correlates with cytokine imbalance in AS. It may serve as a valuable immunotherapeutic target for AS. MSCs can significantly inhibit monocyte-mediated inflammatory response potentially by downregulating MPO in monocytes.

Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disease with unclear etiology and pathogenesis. Mesenchymal stem cell (MSC) and MSC derived extracellular vesicles (EVs) play important roles in regulating innate and adaptive immunity, which are involved in many physiological and pathological processes and contribute to the immune homeostasis in SLE. The effects of MSCs and EVs on SLE have been drawing more and more attention during the past few years. This article reviews the immunomodulatory effects and underlying mechanisms of MSC/MSC-EVs in SLE, which provides novel insight into understanding SLE pathogenesis and guiding the biological therapy.

The mechanical properties of materials are fundamentally determined by the behavior of atomic bonds under stress. Probing bond behavior during deformation, however, is highly challenging, particularly for materials with complex chemical compositions and/or atomic structures, such as metallic glasses (MGs). As a result, a significant gap exists in the current understanding of the mechanical properties of MGs in relation to the atomic bond behavior and how this relationship is influenced by metallurgical factors (e.g., alloy composition, processing conditions). Here, we present our study of the compositional effects on the tensile behavior of atomic bonds in Cu93−xZrxAl7 (x = 40, 50, 60 at.%) MGs using large-scale molecular dynamics (MD) simulations and statistical analysis. Specifically, we examine the populations (fractions), mean bond lengths, mean bond z-lengths, and mean bond z-strains of the different bond types before and during tensile loading (in the z-direction), and we compare these quantities across the different alloy compositions. Among our key findings, we show that increasing the Zr content in the alloy composition leads to shortened Zr-Zr, Al-Cu, Al-Zr, and Cu-Zr bonds and elongated Cu-Cu bonds, as evidenced by their mean bond lengths. During deformation, the shorter Zr-Zr bonds and longer Cu-Cu bonds in the higher-Zr-content alloys, compared with those in the x = 40 alloy, appear stronger (more elastic stretching in the z-direction) and weaker (less z-stretching), respectively, consistent with general expectations. In contrast, the Al-Cu, Al-Zr, and Cu-Zr bonds in the higher-Zr-content alloys appear weaker in the elastic regime, despite their shortened mean bond lengths. This apparent paradox can be reconciled by considering the fractions of these bonds associated with icosahedral clusters, which are known to be more resistant to deformation than the rest of the glassy structure. We also discuss how the compositional effects on the bond behavior relate to variations in the overall stress–strain behavior of the different alloys.

Multicomponent metallic glasses (MGs) are a fascinating class of advanced alloys known for their exceptional properties such as limit-approaching strength, high hardness and corrosion resistance, and near-net-shape castability. One important question regarding these materials that remains unanswered is how the different elements and atomic bonds within them control their strength and deformability. Here, we present a detailed visual and statistical analysis of the behaviors of various elements and atomic bonds in the Zr47Cu46Al7 (at%) MG during a uniaxial tensile test (in the z-direction) simulated using molecular dynamics. Specifically, we investigate the identities of atoms undergoing significant shear strain, and the averaged bond lengths, projected z-lengths, and z-angles (angles with respect to the z-direction) of all the atomic bonds as functions of increasing strain. We show that, prior to yielding, the Zr element and the intermediate (Zr-Zr, Cu-Al) and stronger (Zr-Al, Zr-Cu) bonds dominate the elastic deformation and strength, while the Cu and Al elements and the weaker Al-Al and Cu-Cu bonds contribute more to the highly localized shear transformation. The significant reconstruction, as signified by the cessation of bond-length increment and bond-angle decrement, of the intermediate and the stronger bonds triggers yielding of the material. After yielding, all the elements and bonds participate in the plastic deformation while the stronger bonds contribute more to the residual strength and the ultimate (fracture) strain. The results provide new insights into the atomic mechanisms underlying the mechanical behavior of multicomponent MGs, and may assist in the future design of MG compositions towards better combination of strength and deformability.