The regulation of cardiac muscle contraction must differ from that of skeletal muscles to effect different physiological and contractile properties. Cardiac troponin C (TnC), the key regulator of cardiac muscle contraction, possesses different functional and Ca 2؉ -binding properties compared with skeletal TnC and features a Ca 2؉ -binding site I, which is naturally inactive. The structure of cardiac TnC in the Ca 2؉ -saturated state has been determined by nuclear magnetic resonance spectroscopy. The regulatory domain exists in a "closed" conformation even in the Ca 2؉ -bound (the "on") state, in contrast to all predicted models and differing significantly from the calcium-induced structure observed in skeletal TnC. This structure in the Ca 2؉

Objective Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication. Methods Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA–no ILD, RA–mild ILD, or RA–advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest. Results MMP-7 and interferon-γ–inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA–no ILD, 41 RA-ILD, 42 RA–indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA–no ILD, 49 RA-ILD, 15 RA–indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses. Conclusion Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.

Objectives. Asymptomatic and symptomatic patients may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their clinical features and immune responses remain largely unclear. We aimed to characterise the clinical features and immune responses of asymptomatic and symptomatic patients infected with SARS-CoV-2. Methods. We collected clinical, laboratory and epidemiological records of patients hospitalised in a coronavirus field hospital in Wuhan. We performed qualitative detection of anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) using archived blood samples. Results. Of 214 patients with SARS-CoV-2, 26 (12%) were asymptomatic at hospital admission and during hospitalisation. Most asymptomatic patients were ≤ 60 years (96%) and females (65%) and had few comorbidities (< 16%). Serum levels of white and red blood cells were higher in asymptomatic than in symptomatic patients (Pvalues < 0.05). During hospitalisation, IgG seroconversion was commonly observed in both asymptomatic and symptomatic patients (85% versus 94%, P-value = 0.07); in contrast, IgM seroconversion was less common in asymptomatic than in symptomatic patients (31% versus 74%, P-value < 0.001). The median time from the first virus-positive screening to IgG or IgM seroconversion was significantly shorter in asymptomatic than in symptomatic patients (median: 7 versus 14 days, P-value < 0.01). Furthermore, IgG/IgM seroconversion rates increased

Our results indicate that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have more severe disease activity and more frequent renal involvement and LSLE patients have milder disease activity, more commonly accompanied by Sjögren's syndrome, at disease onset.