The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.

No abstract

The aim of the study was to investigate the characteristics of adult clinically amyopathic dermatomyositis (CADM) with rapid progressive interstitial lung disease (ILD). Hospitalized patients with dermatomyositis (DM) and polymyositis (PM) between 1998 and 2005 in the Shanghai Renji Hospital were retrospectively studied. One hundred and forty-five patients were classified into CADM, classic DM or PM according to the modified Sontheimer's definition or Bohan-Peter's classification criteria. They were further stratified based on the presence or absence of clinical ILD. The Kaplan-Meier survival analysis and COX regression were performed. The predictive factors for ILD and other clinical properties of CADM-ILD were explored. The presence of clinical ILD was a significant risk factor for the poor outcome of DM/PM (OR = 4.237, CI 95%: 1.239-14.49, p = 0.021). Other risk factors are the presence of rashes and elevated urea nitrogen. Patients with DM/PM complicated by ILD had different clinical courses. Patients with CADM-ILD showed a rapidly progressive pattern with 6-month survival rate of 40.8%. The DM-ILD manifested a progressive pattern with a 5-year survival rate of 54%, while PM-ILD was chronic with 5- and 10-year survival rate of 72.4% and 60.3%, respectively. Better preserved muscle strength, elevated erythrocyte sedimentation rate, and hypoalbuminemia may herald ILD in DM/PM. Patients with CADM-ILD who later died had lower PO(2), higher lactate dehydrogenase, and prominent arthritis/arthralgia compared with those who survived. The presence of antinuclear antibody seems to be protective. Rapid progressive CADM-ILD is refractory to conventional treatment. ILD is a common complication in over 40% of our hospitalized DM/PM cohort and is also a prominent prognostic indicator. CADM is a special phenotype of DM/PM. CADM-ILD, which is usually rapidly progressive and fatal, requires further investigation.

No abstract

BACKGROUND: The prognosis of amyopathic dermatomyositis (ADM)-associated interstitial lung disease (ILD) is poor. A mortality risk score model is needed to predict survival in patients with ADM-ILD and to guide clinical treatment. RESEARCH QUESTION: How to identify patients with ADM-ILD who are at high risk and to predict patient outcome based on a risk stratification model? STUDY DESIGN AND METHODS: We evaluated 207 patients with ADM-ILD in this prospective inception study. We used a multivariable Cox proportional hazards model to identify the independent prognostic risk factors and created a risk score model according to patient data from January 2012 to December 2016. We used the index of prediction accuracy that uses the Brier score to reflect both discrimination and calibration of the model. The model was validated in an independent group of patients from January 2017 to June 2018. RESULTS: We developed a combined risk score, the FLAIR score, that included the following values and scores: ferritin (<636 ng/mL, 0; $636 ng/mL, 2), lactate dehydrogenase (<355 U/ L, 0; $355 U/L, 2), antimelanoma differentiation-associated gene 5 antibody (negative, 0; þ, 2; þþ, 3; þþþ, 4), high-resolution CT imaging score (<133, 0; $133, 3), and rapidly progressive ILD (RPILD) (non-RPILD, 0; RPILD, 2). We divided patients into three risk groups according to the FLAIR score: low, 0 to 4; medium, 5 to 9; and high, 10 to 13. In both discovery and validation cohorts, high-risk patients had significantly higher mortality rates than low-and medium-risk patients (P < .001). INTERPRETATION: The FLAIR risk score model could help to predict survival in patients with ADM-ILD and to guide further clinical research on risk-based treatment.

Lipopolysaccharide (LPS) derived from Gram-negative bacteria activates plasma membrane signaling via Toll-like receptor 4 (TLR4) on host cells and triggers innate inflammatory responses, but the underlying mechanisms remain to be fully elucidated. Here we reveal a role for annexin A2 (AnxA2) in host defense against infection as anxa2−/− mice were highly susceptible to Gram-negative bacteria-induced sepsis with enhanced inflammatory responses. Computing analysis and biochemical experiments identified that constitutive AnxA2 expression facilitated TLR4 internalization and its subsequent translocation into early endosomal membranes. It activated the TRAM-dependent endosomal signaling, leading to the release of anti-inflammatory cytokines. Importantly, AnxA2 deficiency prolonged TLR4-mediated signaling from the plasma membrane, which was attributable to pro-inflammatory cytokine production (IL-6, TNFα and IL-1β). Thus, AnxA2 directly exerted negative regulation of inflammatory responses through TLR4-initiated TRAM-TRIF pathway occurring on endosomes. This study reveals AnxA2 as a critical regulator in infection-initiated inflammation, which protects the host from excessive inflammatory damage.

Metabolic fingerprints of biofluids encode diverse diseases and particularly urine detection offers complete noninvasiveness for diagnostics of the future.P resent urine detection affords unsatisfactory performance and requires advanced materials to extract molecular information, due to the limited biomarkers and high sample complexity.Herein, we report plasmonic polymer@Ag for laser desorption/ionization mass spectrometry (LDI-MS) and sparse-learning-based metabolic diagnosis of kidney diseases.U sing only 1 mLo fu rine without enrichmento rp urification, polymer@Ag afforded urine metabolic fingerprints (UMFs) by LDI-MS in seconds. Analysis by sparse learning discriminated lupus nephritis from various other non-lupus nephropathies and controls.W e combined UMFs with urine protein levels (UPLs) and constructed an ew diagnostic model to characterizes ubtypes of kidney diseases.Our work guides urine-based diagnosis and leads to new personalized analytical tools for other diseases.

Cyclic GMP-AMP (cGAMP) synthase (cGAS, a.k.a. MB21D1), a cytosolic DNA sensor, catalyzes formation of the second messenger 2’3’-cGAMP that activates the stimulator of interferon genes (STING) signaling. How the cGAS activity is modulated remains largely unknown. Here, we demonstrate that sentrin/SUMO-specific protease 7 (SENP7) interacted with and potentiated cGAS activation. The small ubiquitin-like modifier (SUMO) was conjugated onto the lysine residues 335, 372 and 382 of cGAS, which suppressed its DNA-binding, oligomerization and nucleotidyl-transferase activities. SENP7 reversed this inhibition via catalyzing the cGAS de-SUMOylation. Consistently, silencing of SENP7 markedly impaired the IRF3-responsive gene expression induced by cGAS-STING axis. SENP7-knockdown mice were more susceptible to herpes simplex virus 1 (HSV-1) infection. SENP7 was significantly up-regulated in patients with SLE. Our study highlights the temporal modulation of the cGAS activity via dynamic SUMOylation, uncovering a novel mechanism for fine-tuning the STING signaling in innate immunity.