Mycophenolate Mofetil and New-Onset Systemic Lupus Erythematosus: A Randomized Clinical Trial.

Importance: Anti-double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear. Objective: To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE. Design, Setting, and Participants: This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022. Interventions: Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses. Results: Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug-related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group). Conclusions and Relevance: The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800017540.

Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury.

Objectives: Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through in vivo and in vitro studies. Methods: Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. Results: After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Conclusion: Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.

Transient Expression Vector Construction, Subcellular Localisation, and Evaluation of Antiviral Potential of Flagellin BP8-2.

This study used the DNA of Bacillus amyloliquefaciens Ba168 as a template to amplify the flagellin BP8-2 gene and ligate it into the fusion expression vector pCAMBIA1300-35S-EGFP after digestion for the construction of the expression vector pCAMBIA1300-EGFP-BP8-2. Next, using Nicotiana benthamiana as receptor material, transient expression was carried out under the mediation of Agrobacterium tumefaciens C58C1. Finally, the transient expression and subcellular localisation of flagellin BP8-2 protein were analysed using the imaging of co-transformed GFP under laser confocal microscopy. The results showed that flagellin BP8-2 was localised in the cell membrane and nucleus, and the RT-PCR results showed that the BP8-2 gene could be stably expressed in tobacco leaf cells. Furthermore, there was stronger antiviral activity against tobacco mosaic virus (TMV) infection in Nicotiana glutinosa than in BP8-2 and ningnanmycin, with an inhibitory effect of 75.91%, protective effect of 77.45%, and curative effect of 68.15%. TMV movement and coat protein expression were suppressed, and there was a high expression of PR-1a, PAL, and NPR1 in BP8-2-treated tobacco leaf. These results suggest that flagellin BP8-2 inhibits TMV by inducing resistance. Moreover, BP8-2 has low toxicity and is easily biodegradable and eco-friendly. These results further enrich our understanding of the antiviral mechanisms of proteins and provide alternatives for controlling viral diseases in agriculture.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

Neutrophil activation biomarker pentraxin 3 for diagnosis and monitoring of macrophage activation syndrome occurrence in adult-onset Still's disease.

Macrophage activation syndrome (MAS) is a potentially fatal consequence of adult-onset Still's disease (AOSD), driven by a cytokine storm. Efficient early diagnosis of AOSD-associated MAS requires a sensitive and specific biomarker. In this study, we demonstrated that pentraxin 3 (PTX3), an acute phase protein, was associated with AOSD disease activity and served as a biomarker for AOSD-MAS. PTX3 levels were significantly increased in AOSD patients compared to other autoimmune diseases and healthy controls. Plasma PTX3 levels showed positive correlations with inflammatory markers, the systemic score and the HScore. In active AOSD with MAS, PTX3 levels were higher compared to those in non-AOSD haemophagocytic lymphohistiocytosis (HLH) patients. Moreover, the PTX3's area under the curve value for distinguishing AOSD with MAS exceeded that of soluble interleukin-2 receptor, ferritin and C-reactive protein. Furthermore, plasma levels of PTX3 were associated with circulating NET-DNA levels. To fully understand the underlying mechanism of PTX3 prompting AOSD and AOSD-MAS progression, we discovered that neutrophils exhibited enhanced NET formation and mitogen-activated protein kinases (MAPK) pathway activation upon PTX3 stimulation. More importantly, PTX3-induced NET formation was effectively dampened by MAPK pathway inhibitors. These findings collectively revealed that PTX3 has a favorable correlation with disease activity and may serve as a potential biomarker to differentiate AOSD patients with MAS. Additionally, PTX3 induces NET release via the MAPK pathway, suggesting a pathogenic role in AOSD-MAS.

Characteristics of COVID-19 and Impact of Disease Activity in Patients with Adult-Onset Still's Disease.

INTRODUCTION: This study aimed to characterize the morbidity, hospitalization, and mortality rates among patients with adult-onset Still's disease (AOSD) affected by coronavirus disease 2019 (COVID-19) and explore the impact of COVID-19 on the disease activity of AOSD. METHODS: Data on the clinical and demographic characteristics, COVID-19-related symptoms, and outcomes were retrospectively collected. Patients were stratified according to COVID-19 severity and associations between risk factors and outcomes were analyzed using multivariate logistic regression. The disease activity of patients with AOSD flares after COVID-19 was described. RESULTS: A total of 188 patients with AOSD were followed up, of whom 75.5% (n = 142) had a confirmed or highly suspected COVID-19. Patients on medium or high-dose oral glucocorticoids or Janus kinase (JAK) inhibitors were at increased risk of developing moderate to severe COVID-19. Six patients suffered flares of AOSD following COVID-19 in a short period; however, the relapse rate was not statistically increased compared with patients without COVID-19. CONCLUSION: Patients with AOSD receiving medium or high-dose glucocorticoid therapy or JAK inhibitors had worse COVID-19 outcomes. Further work is needed to explore risk factors affecting COVID-19 outcomes and the impact of COVID-19 on disease activity in AOSD.

Neutralizing anti-IFN-γ IgG was increased in patients with systemic lupus erythematosus and associated with susceptibility to infection.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complicated autoimmune disease, in which infection is a leading cause of death. Some SLE patients clinically presented with recurrent and refractory infections, which manifested as adult-onset immunodeficiency syndrome due to the production of anti-interferon-γ (anti-IFN-γ) autoantibodies. This study aimed to investigate the role of anti-IFN-γ autoantibodies concerning severe infections in SLE patients. METHODS: We detected serum levels of anti-IFN-γ IgG/IgM isotypes in SLE patients with severe infections (n = 55), SLE patients without severe infections (n = 120), rheumatoid arthritis (n = 24), ankylosing spondylitis (n = 24), and healthy controls (n = 60). The relationship between anti-IFN-γ autoantibodies and clinical characteristics and laboratory parameters were analyzed. We further evaluated the neutralizing ability of anti-IFN-γ IgG. RESULTS: The level of anti-IFN-γ IgG was significantly elevated in SLE patients with severe infections compared with the other groups (all p < 0.01), and the positive rates of anti-IFN-γ IgG in SLE patients with and without severe infections were 29.1% and 10.8%, respectively. Further analysis indicated that the levels of anti-IFN-γ IgG were positively associated with the SLEDAI score (r = 0.6420, p < 0.001), and it could predict the susceptibility to severe infections in SLE patients. Moreover, the inhibition and function assay showed that purified IgG from anti-IFN-γ IgG-positive SLE patients could neutralize IFN-γ, and further impair IFN-γ-induced STAT1 phosphorylation. CONCLUSIONS: The neutralizing anti-IFN-γ IgG might increase the susceptibility to infection in SLE patients, which has important implications for the treatment. Key Points • The role of anti-IFN-γ autoantibodies concerning severe infections in SLE patients remains unknown. • The results of this study reveals that anti-IFN-γ IgG levels were significantly elevated in SLE patients with severe infections. • This study suggests that neutralizing anti-IFN-γ IgG might increase the susceptibility to infection in SLE patients.

2023 International Consensus Guidance for the use of Tripterygium Wilfordii Hook F in the treatment of active rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints and produces pain, swelling, and stiffness. It has a lifetime prevalence of up to 1% worldwide. An extract of Tripterygium wilfordii Hook F (TwHF), a member of the Celastraceae herbal family widely available in south China, has been used for treatment of RA since 1960s. METHODS: The current consensus practice guidance (CPG) aims to offer guidance on the application of TwHF in the clinical management of active RA. The CPG followed World Health Organisation (WHO)'s recommended process, carried out three systematic reviews to synthesize data from 19 randomised controlled trials (RCT) involving 1795 participants. We utilized Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to evaluate certainty of evidence and derive recommendations. We rigorously followed The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as conduct guides to minimise bias and promote transparency. RESULTS: There was no obvious difference between TwHF monotherapy and methotrexate (MTX) monotherapy on ACR20 (RCT = 2, N = 390, RR = 1.06, 95%CI 0.90-1.26, moderate certainty), ACR50 (RCT = 3, N = 419, RR = 1.03, 95%CI 0.80-1.34, moderate certainty), ACR70 (RCT = 2, N = 390, RR = 1.12, 95%CI 0.69-1.79, low certainty). TwHF monotherapy may be better than salicylazosulfapyridine monotherapy on ACR20 and the effect may be similar on ACR50 and ACR70. Seven RCTs compared MTX combined with TwHF versus MTX monotherapy, and the meta-analysis results favoured combination therapy group on ACR20 (RCT = 3, N = 470, RR = 1.44, 95%CI 1.28-1.62, moderate certainty), ACR50 (RCT = 4, N = 500, RR = 1.88, 95%CI 1.56-2.28, moderate certainty) and ACR70 (RCT = 2, N = 390, RR = 2.12, 95%CI 1.40-3.19, low certainty). We found no obvious difference between groups on critical safety outcomes, including infection (RCT = 3, N = 493, RR = 1.37, 95%CI 0.84-2.23), liver dysfunction (RCT = 5, N = 643, RR = 1.14, 95%CI 0.71-1.85), renal damage (RCT = 3, N = 450, RR = 2.20, 95%CI 0.50-9.72). CONCLUSION: Upon full review of the evidence, the guidance panel reached consensus on recommendations for the use of TwHF in people with active RA, either as monotherapy or as combination therapy with MTX.

Neutrophil extracellular trap-induced intermediate monocytes trigger macrophage activation syndrome in adult-onset Still's disease.

BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease characterized by innate immune system activation, with a high risk for macrophage activation syndrome (MAS). MAS development is associated with monocyte/macrophage activation and cytokine storm. Monocytes consist of three different subsets, classical monocytes (CMs, CD14brightCD16 -), intermediate monocytes (IMs, CD14brightCD16 +), and non-classical monocytes (NCMs, CD14dimCD16 +), each has distinct roles in inflammatory regulation. However, the frequencies and regulatory mechanism of monocyte subsets in AOSD patients have not been identified. METHODS: We performed flow cytometry, RNA sequencing, phagocytosis analysis, and enzyme-linked immunosorbent assay to evaluate monocyte subsets, cell functions, and potential biomarkers. The effect of neutrophil extracellular traps (NETs) on monocytes was determined by evaluating mRNA levels of DNA sensors, surface CD16 expression, and inflammasome pathway activation. RESULTS: Higher proportions of intermediate monocytes (IMs) were identified in active AOSD patients. IMs displayed higher expression of CD80, CD86, HLA-DR, and CD163 than CMs and NCMs. CD163 upregulation was noted on AOSD IMs, accompanied by increased phagocytic activity and elevated cytokine/chemokine production, including IL-1ß, IL-6, CCL8, and CXCL10. The frequencies of IMs were correlated with disease activity and higher in AOSD patients with MAS (AOSD-MAS). CCL8 and CXCL10 were highly expressed in RNA sequencing of monocytes from AOSD-MAS patients and plasma CXCL10 level could serve as a potential biomarker for AOSD-MAS. Moreover, DNA-sensing pathway was activated in monocytes from AOSD-MAS patients. Stimulation with NETs derived from AOSD induced DNA sensor expression, the expansion of IMs, and inflammasome pathway activation. These effects can be abrogated by DNase I treatment. CONCLUSIONS: Our results demonstrated that the proportions of IMs were elevated in AOSD and associated with MAS. The DNA component in NETs from AOSD plays an important role in the formation of IMs, shedding new light for the therapeutic target.

Analysis of Bioactive Compounds Produced by Bacillus mojavensis ZA1 and Their Antagonistic Effect on Colletotrichum coccodes by GC-MS.

The plant disease Colletotrichum coccodes, which lowers potato yields, poses a severe danger to the booming potato industry. Isolated plant endophytic bacteria from highland pasture can produce a variety of metabolites that lessen the risk that the pathogen C. coccodes poses to plant growth and development. Therefore, the objective of our work was to assess substances with antipathogenic properties made by the endophytic bacteria Bacillus mojavensis ZA1. Gas chromatography-mass spectrometry (GC-MS) was used in our investigation to accomplish a thorough structural elucidation of the antipathogenic compounds produced by the endophytic bacterial strain B. mojavensis ZA1. The results showed that the metabolites extracted from ethyl acetate as an extractant were the most effective in inhibiting the pathogen C. coccodes, with 60.95% inhibition. Thirty-five distinct chemicals, including acids, esters, ketones, alcohols, amino acid ammonium salts, cyclic ethers, aromatic hydrocarbons, and heterocyclic compounds, were among the metabolites that may inhibit C. coccodes. Further analysis of the chemical groups in the compound structures revealed the potential of driving groups, such as hydroxyl, carbonyl, ester, benzene, carbon-carbon double bonds, and carbon rings, that prevent C. coccodes from performing its function. This study opens up new opportunities for plant protection programs by demonstrating that natural chemicals produced by B. mojavensis ZA1 can be used as candidates for cutting-edge plant disease management treatments.

Beyond the classics: The emerging value of anti-phosphatidylserine/prothrombin antibodies in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs), which can lead to thrombosis and pregnancy complications. Within the diverse range of aPLs, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) have gained significance in clinical practice. The detection of aPS/PT has proven valuable in identifying APS patients and stratifying their risk, especially when combined with other aPL tests like lupus anticoagulant (LA) and anti-ß2-glycoprotein I (aß2GPI). Multivariate analyses have confirmed aPS/PT as an independent risk factor for vascular thrombosis and obstetric complications, with its inclusion in the aPL score and the Global Anti-Phospholipid Syndrome Score (GAPSS) aiding in risk evaluation. However, challenges remain in the laboratory testing of aPS/PT, including the need for assay standardization and its lower sensitivity in certain patient populations. Further research is necessary to validate the clinical utility of aPS/PT antibodies in APS diagnosis, risk stratification, and management.

The use of high-sensitivity cardiac troponin I in assessing cardiac involvement and Disease prognosis in idiopathic inflammatory myopathy.

OBJECTIVES: Cardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients. METHODS: A total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis. RESULTS: Higher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962-31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis. CONCLUSIONS: Serum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis.

The landscape of innate and adaptive immune cell subsets in patients with adult-onset Still's disease.

OBJECTIVE: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder. The understanding of the changes in adaptive immune cells and the crosstalk between innate and adaptive immune systems in AOSD is limited. This study aimed to examine the peripheral immune cell composition and inflammatory protein levels in AOSD patients. METHODS: Twenty-nine active AOSD patients were enrolled. Flow cytometry was used to analyze the cell populations in peripheral blood. Antibody chips were utilized to detect the protein expression profile in serum. RESULTS: In active AOSD patients, there was an increase in the percentage of classical and non-classical monocytes among peripheral blood mononuclear cells. The proportion of natural killer (NK) cells decreased, with an increase in CD56dim NK1 cells and a decrease in CD56bright NK2 cells compared with healthy controls (HC). The percentage of naïve central memory T cells was decreased, while the percentage of effector and effector memory T cells was increased among adaptive lymphocytes. The proportion of naïve B and memory B cells was decreased, while plasma cells were increased in AOSD patients, indicating activation of the adaptive immune system. Additionally, the serum levels of 40 proteins were elevated in AOSD patients, primarily involved in cytokine-cytokine receptor interaction, inflammatory response, and regulation of MAPK cascade. CONCLUSION: Our findings showed the activation of the innate and adaptive immune system in AOSD. The protein-protein interaction analysis suggested potential communication between innate and adaptive cell subsets. These findings provide new insights into the pathogenesis of the disease and the development of targeted therapies.

Risk factors in antiphospholipid antibody-associated valvular heart disease: A 383-patient cohort study.

Valvular heart disease (VHD) is a prevalent cardiac manifestation in antiphospholipid syndrome (APS) patients. However, risk factors and predictors for antiphospholipid antibody-associated VHD (aPL-VHD) remain vague. We aimed to assess the risk of developing aPL-VHD in aPL-positive patients, by establishing a clinical prediction model upon a cross-sectional cohort from APS-Shanghai database, including 383 APS patients and durable aPL carriers with transthoracic echocardiography investigation. The prevalence of aPL-VHD was 11.5%. Multivariate logistic regression analysis identified three independent risk factors for aPL-VHD: anti-ß2GPI IgG (OR 5.970, P < 0.001), arterial thrombosis (OR 2.758, P = 0.007), and stratified estimated glomerular filtration rate levels (OR 0.534, P = 0.001). A prediction model for aPL-VHD, incorporating the three factors, was further developed, which demonstrated good discrimination with a C-index of 0.855 and 0.841 (after bootstrapping), and excellent calibration (P = 0.790). We provide a practical tool for assessing the risk of developing VHD among aPL-positive patients.

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis.

Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.

Value of the HFA-PEFF diagnostic algorithms for heart failure with preserved ejection fraction to the inflammatory myopathy population.

OBJECTIVES: The HFA-PEFF score has been validated to hold great diagnostic and prognostic utility for heart failure with preserved ejection fraction (HFpEF). Idiopathic inflammatory myopathy (IIM) is recognized as one of the potential etiologies underlying HFpEF. Here, we intended to investigate the real prevalence of HFpEF in IIM via the HFA-PEFF score and explore the prognostic value of this score. METHODS: Two hundred twenty IIM patients were enrolled for assessment. The cohort was divided into low, intermediate and high tertiles of the HFA-PEFF score. Spearman's correlation analysis was used to explore the association between the score and disease activity. Chi-square test was applied to investigate the distribution discrepancy of HFA-PEFF tertiles among patients with different myositis-specific antibodies (MSAs) or myositis-associated antibodies (MAAs). Univariate and multivariate ordinal regression analyses were performed to screen risk factors for high HFA-PEFF scores. Survival curves were obtained using the Kaplan-Meier method and log-rank tests. RESULTS: In total, 79 (35.9%), 107 (48.6%) and 34 (15.5%) patients were rated low, intermediate and high probability of HFpEF, respectively. The HFA-PEFF score correlated well with disease activity. Patients with positive AMA-M2 scored higher in the HFA-PEFF score (p = 0.011). During follow-up, patients with positive AMA-M2 or anti-SRP antibody developed an inclination towards concentric hypertrophy on echocardiography. Additionally, palpitation symptom, AMA-M2 positivity and elevated serum levels of LDH, cTnI were independent risk factors for high HFA-PEFF scores. Finally, a high-tertile HFA-PEFF score was related to lower overall survival rate (p < 0.001). Patients with positive AMA-M2 had poorer outcomes (p = 0.002). CONCLUSION: HFpEF was prevailing in IIM patients according to the HFA-PEFF score. The HFA-PEFF score correlated well with disease activity and held significant prognostic value. Patients with AMA-M2 antibody were prone to have poor outcomes.

Molecular Identification and Characterization of Fusarium Associated with Walnut Branch Blight Disease in China.

In October 2020, samples of walnut branch blight were collected from Longnan. Pathogens were isolated and identified based on morphological and molecular features, and their characteristics were analyzed by pathogenicity. Pathogenicity testing revealed that seven strains (LN-1, LN-3, LN-6, LN-19, LN-27, QY3-1, and QY9-1) induced symptoms of walnut branch blight that were consistent with those observed in the field after inoculation. Furthermore, some Fusarium-type conidia and spherical chlamydospores were visible indicating that they were Fusarium spp. A molecular characterization including sequence and phylogenetic analysis of the ITS, TEF-1α, ßTUB, Fu, and LSU gene regions revealed that LN-1 and LN-19 belonged to F. avenaceum, LN-3 and LN-6 to F. acuminatum, LN-27 to F. sporotrichioides, and QY3-1 and QY9-1 to F. tricinctum. This is the first time that F. acuminatum-, F. sporotrichioides-, and F. tricinctum-caused walnut branch blight has been reported in China.