The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review

Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells and tissues. However, the pathogenesis of autoimmune diseases has not been clearly elucidated. The activation, differentiation, and development of CD8+ T cells can be affected by numerous inflammatory cytokines, transcription factors, and chemokines. In recent years, epigenetic modifications have been shown to play an important role in the fate of CD8+ T cells. The discovery of these modifications that contribute to the activation or suppression of CD8+ cells has been concurrent with the increasing evidence that CD8+ T cells play a role in autoimmunity. These relationships have been studied in various autoimmune diseases, including multiple sclerosis (MS), systemic sclerosis (SSc), type 1 diabetes (T1D), Grave's disease (GD), systemic lupus erythematosus (SLE), aplastic anemia (AA), and vitiligo. In each of these diseases, genes that play a role in the proliferation or activation of CD8+ T cells have been found to be affected by epigenetic modifications. Various cytokines, transcription factors, and other regulatory molecules have been found to be differentially methylated in CD8+ T cells in autoimmune diseases. These genes are involved in T cell regulation, including interferons, interleukin (IL),tumor necrosis factor (TNF), as well as linker for activation of T cells (LAT), cytotoxic T-lymphocyte–associated antigen 4 (CTLA4), and adapter proteins. MiRNAs also play a role in the pathogenesis of these diseases and several known miRNAs that are involved in these diseases have also been shown to play a role in CD8+ regulation

Tuning redox active polyoxometalates for efficient electron‐coupled proton buffer mediated water splitting

We present strategies to tune the redox properties of polyoxometalate clusters to enhance the electron‐coupled proton‐buffer‐mediated water splitting process, in which the evolution of hydrogen and oxygen can occur in different forms and is separated in time and space. By substituting the heteroatom template in the Keggin‐type polyoxometalate cluster, H6ZnW12O40, it is possible to double the number of electrons and protonation in the redox reactions (from two to four). This increase can be achieved with better matching of the energy levels as indicated by the redox potentials, compared to the ones of well‐studied H3PW12O40 and H4SiW12O40. This means that H6ZnW12O40 can act as a high‐performance redox mediator in an electrolytic cell for the on‐demand generation of hydrogen with a high decoupling efficiency of 95.5 % and an electrochemical energy efficiency of 83.3 %. Furthermore, the H6ZnW12O40 cluster also exhibits an excellent cycling behaviour and redox reversibility with almost 100 % H2‐mediated capacity retention during 200 cycles and a high coulombic efficiency >92 % each cycle at 30 mA cm−2

In-situ growth of nitrogen-doped carbon nanotubes on MXene nanosheets for efficient sodium/potassium-ion storage

For game changing for future of large-scale energy storage technologies, sodium-ion and potassium-ion batteries provide a substitute to lithium-ion batteries. As an excellent candidate anode, MXene still suffers from the blockage of active sites caused by restacking of sheets. Herein, an in-situ decoration of MXene nanosheets with nitrogen-doped carbon nanotubes (CNTs) is introduced, to yield MXene@CNTs. The modification of nitrogen-doped CNTs not only prevents the restacking of MXene and increases ion accessibility but also improves the electrode’s overall conductivity, thereby enhancing electron conduction and ion diffusion kinetics significantly. Therefore, MXene@CNTs exhibits superior sodium/potassium-ion storage performance than pure MXene nanosheets. At 0.05 A g-1, it can deliver reversible capacities of 286 mAh g-1 for SIBs and 250 mAh g-1 for PIBs. This research illustrates the significance of the electrode architecture for electrochemical performances, and the in-situ growth strategy could provide some insight on searching for high-performance MXene-based anodes for SIBs and PIBs

How does the recurrence-related morphology characteristics of the Pcom aneurysms correlated with hemodynamics?

IntroductionPosterior communicating artery (Pcom) aneurysm has unique morphological characteristics and a high recurrence risk after coil embolization. This study aimed to evaluate the relationship between the recurrence-related morphology characteristics and hemodynamics.MethodA total of 20 patients with 22 Pcom aneurysms from 2019 to 2022 were retrospectively enrolled. The recurrence-related morphology parameters were measured. The hemodynamic parameters were simulated based on finite element analysis and computational fluid dynamics. The hemodynamic differences before and after treatment caused by different morphological features and the correlation between these parameters were analyzed.ResultSignificant greater postoperative inflow rate at the neck (Qinflow), relative Qinflow, inflow concentration index (ICI), and residual flow volume (RFV) were reported in the aneurysms with wide neck (>4 mm). Significant greater postoperative RFV were reported in the aneurysms with large size (>7 mm). Significant greater postoperative Qinflow, relative Qinflow, and ICI were reported in the aneurysms located on the larteral side of the curve. The bending angle of the internal carotid artery at the initiation of Pcom (αICA@PCOM) and neck diameter had moderate positive correlations with Qinflow, relative Qinflow, ICI, and RFV.ConclusionThe morphological factors, including aneurysm size, neck diameter, and αICA@PCOM, are correlated with the recurrence-inducing hemodynamic characteristics even after fully packing. This provides a theoretical basis for evaluating the risk of aneurysm recurrence and a reference for selecting a surgical plan

Direct evidence for cosmic-ray-induced correlated errors in superconducting qubit array

Correlated errors can significantly impact the quantum error correction, which challenges the assumption that errors occur in different qubits independently in both space and time. Superconducting qubits have been found to suffer correlated errors across multiple qubits, which could be attributable to ionizing radiations and cosmic rays. Nevertheless, the direct evidence and a quantitative understanding of this relationship are currently lacking. In this work, we propose to continuously monitor multi-qubit simultaneous charge-parity jumps to detect correlated errors and find that occur more frequently than multi-qubit simultaneous bit flips. Then, we propose to position two cosmic-ray muon detectors directly beneath the sample box in a dilution refrigerator and successfully observe the correlated errors in a superconducting qubit array triggered by muons. By introducing a lead shielding layer on the refrigerator, we also reveal that the majority of other correlated errors are primarily induced by gamma rays. Furthermore, we find the superconducting film with a higher recombination rate of quasiparticles used in the qubits is helpful in reducing the duration of correlated errors. Our results provide experimental evidence of the impact of gamma rays and muons on superconducting quantum computation and offer practical insights into mitigation strategies for quantum error correction. In addition, we observe the average occurrence rate of muon-induced correlated errors in our processor is approximately 0.40 min$^{-1}$cm$^{-2}$, which is comparable to the muon event rate detected by the muon detector with 0.506 min$^{-1}$cm$^{-2}$. This demonstrates the potential applications of superconducting qubit arrays as low-energy threshold sensors in the field of high-energy physics.Comment: 7 pages and 5 figures for the main text, 20 pages and 20 figures for the supplementary material

Mendelian randomization and transcriptome analysis identified immune-related biomarkers for osteoarthritis

BackgroundThe immune microenvironment assumes a significant role in the pathogenesis of osteoarthritis (OA). However, the current biomarkers for the diagnosis and treatment of OA are not satisfactory. Our study aims to identify new OA immune-related biomarkers to direct the prevention and treatment of OA using multi-omics data.MethodsThe discovery dataset integrated the GSE89408 and GSE143514 datasets to identify biomarkers that were significantly associated with the OA immune microenvironment through multiple machine learning methods and weighted gene co-expression network analysis (WGCNA). The identified signature genes were confirmed using two independent validation datasets. We also performed a two-sample mendelian randomization (MR) study to generate causal relationships between biomarkers and OA using OA genome-wide association study (GWAS) summary data (cases n = 24,955, controls n = 378,169). Inverse-variance weighting (IVW) method was used as the main method of causal estimates. Sensitivity analyses were performed to assess the robustness and reliability of the IVW results.ResultsThree signature genes (FCER1G, HLA-DMB, and HHLA-DPA1) associated with the OA immune microenvironment were identified as having good diagnostic performances, which can be used as biomarkers. MR results showed increased levels of FCER1G (OR = 1.118, 95% CI 1.031-1.212, P = 0.041), HLA-DMB (OR = 1.057, 95% CI 1.045 -1.069, P = 1.11E-21) and HLA-DPA1 (OR = 1.030, 95% CI 1.005-1.056, P = 0.017) were causally and positively associated with the risk of developing OA.ConclusionThe present study identified the 3 potential immune-related biomarkers for OA, providing new perspectives for the prevention and treatment of OA. The MR study provides genetic support for the causal effects of the 3 biomarkers with OA and may provide new insights into the molecular mechanisms leading to the development of OA

Gene Expression Profiling in Monocytes and SNP Association Suggest the Importance of the Gene for Osteoporosis in Both Chinese and Caucasians

Osteoporosis is characterized mainly by low bone mineral density (BMD). Many cytokines and chemokines have been related with bone metabolism. Monocytes in the immune system are important sources of cytokines and chemokines for bone metabolism. However, no study has investigated in vivo expression of a large number of various factors simultaneously in human monocytes underlying osteoporosis. This study explored the in vivo expression pattern of general cytokines, chemokines, and their receptor genes in human monocytes and validated the significant genes by qRT-PCR and genetic association analyses. Expression profilings were performed in monocyte samples from 26 Chinese and 20 Caucasian premenopausal women with discordant BMD. Genome-wide association analysis with BMD variation was conducted in 1000 unrelated Caucasians. We selected 168 cytokines, chemokines, osteoclast-related factors, and their receptor genes for analyses. Significantly, the signal transducer and activator of transcription 1 (STAT1) gene was upregulated in the low versus the high BMD groups in both Chinese and Caucasians. We also revealed a significant association of the STAT1 gene with BMD variation in the 1000 Caucasians. Thus we conclude that the STAT1 gene is important in human circulating monocytes in the etiology of osteoporosis. © 2010 American Society for Bone and Mineral Research

Etiologic Diagnosis of Lower Respiratory Tract Bacterial Infections Using Sputum Samples and Quantitative Loop-Mediated Isothermal Amplification

Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship

Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells

BACKGROUND: Autophagy is an evolutionarily conserved protein degradation pathway. A defect in autophagy may contribute to tumorigenesis. Autophagy inducers could have a potential function in tumor prevention and treatment. METHODOLOGY/PRINCIPAL FINDINGS: Our results showed that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge Rhabdastrella globostellata, inhibited proliferation of human cancer cell lines Hep3B and A549 and induced caspase-independent cell death in both the cell lines. Further investigation showed that Rhabdastrellic acid-A induced autophagy of cancer cells determined by YFP-LC3 punctation and increased LC3-II. The pretreatment with autophagy inhibitor 3-MA inhibited Rhabdastrellic acid-A-induced cell death. Knockdown of autophagy-related gene Atg5 inhibited Rhabdastrellic acid-A-induced cell death in A549 cells. Also, phospho-Akt and its downstream targets significantly decreased after treatment with Rhabdastrellic acid-A in both cancer cell lines. Transfection of constitutive active Akt plasmid abrogated autophagy and cell death induced by Rhabdastrellic acid-A. CONCLUSIONS/SIGNIFICANCE: These results suggest that Rhabdastrellic acid-A could induce autophagy-associated cell death through blocking Akt pathway in cancer cells. It also provides the evidence that Rhabdastrellic acid-A deserves further investigation as a potential anticancer or cancer preventive agent