Particle Emission-dependent Timing Noise of Pulsars?

Though pulsars spin regularly, the differences between the observed and predicted ToA (time of arrival), known as "timing noise", can still reach a few milliseconds or more. We try to understand the noise in this paper. As proposed by Xu & Qiao in 2001, both dipole radiation and particle emission would result in pulsar braking. Accordingly, possible fluctuation of particle current flow is suggested here to contribute significant ToA variation of pulsars. We find that the particle emission fluctuation could lead to timing noise which can't be eliminated in timing process, and that a longer period fluctuation would arouse a stronger noise. The simulated timing noise profile and amplitude are in accord with the observed timing behaviors on the timescale of years.Comment: 6 pages, 2 figures. (Accepted by Chin. Phys. Lett.

Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection

Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. Conventionally secreted ORF8 is glycosylated and loses the ability to recognize interleukin 17 receptor A of macrophages, possibly due to the steric hindrance imposed by N-glycosylation at Asn78. However, unconventionally secreted ORF8 does not undergo glycosylation without experiencing the ER-Golgi trafficking, thereby activating the downstream NF-κB signaling pathway and facilitating a burst of cytokine release. Furthermore, we show that ORF8 deletion in SARS-CoV-2 attenuates inflammation and yields less lung lesions in hamsters. Our data collectively highlights a role of ORF8 protein in the development of cytokine storms during SARS-CoV-2 infection

In vivo genotoxicity evaluation of crude extract from Ledum palustre and protective effects on cyclophosphamide-induced genotoxicity in mice

Extracts from Ledum palustre (LP) have shown many benefit activities, while, the toxicity of extracts from LP was seldom reported. In the present study, we evaluated the genotoxicity of crude extract from LP. Our results demonstrated that the maximal tolerance dose (MTD) of LP extract was more than 30 g/kg BW in mice (oral). LP extract at doses of 2.5, 5.0 and 10.0 g/kg BW had no genotoxicity in mice and could inhibit cyclophosphamide (CP), a well known anti-tumor drug, induced genotoxicity in mice. LP extract at concentrations of 0.05 g/mL, 0.005 g/mL, and 0.0005 g/ mL had scavenging activity on O2-·in a dose-related way. It was concluded that LP extract had protective effects on CP induced genotoxicity in mice and the protective mechanism of LP extract appeared to be related to antioxidant activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment

Asymptomatic Atrial Fibrillation among Hospitalized Patients:clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients.METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS.CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.</p

Artesunate potentiates antibiotics by inactivating heme-harbouring bacterial nitric oxide synthase and catalase

<p>Abstract</p> <p>Background</p> <p>A current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics. It is urgent to work out a practical solution to combat the multidrug resistant bacterial pathogens.</p> <p>Findings</p> <p>Oxidative stress-acclimatized bacteria thrive in rifampicin by generating antibiotic-detoxifying nitric oxide (NO), which can be repressed by artesunate or an inhibitor of nitric oxide synthase (NOS). Suppressed bacterial proliferation correlates with mitigated NO production upon the combined treatment of bacteria by artesunate with antibiotics. Detection of the heme-artesunate conjugate and accordingly declined activities of heme-harbouring bacterial NOS and catalase indicates that artesunate renders bacteria susceptible to antibiotics by alkylating the prosthetic heme group of hemo-enzymes.</p> <p>Conclusions</p> <p>By compromising NO-mediated protection from antibiotics and triggering harmful hydrogen peroxide burst, artesunate may serve as a promising antibiotic synergist for killing the multidrug resistant pathogenic bacteria.</p

Searching for the nano-Hertz stochastic gravitational wave background with the Chinese Pulsar Timing Array Data Release I

Observing and timing a group of millisecond pulsars (MSPs) with high rotational stability enables the direct detection of gravitational waves (GWs). The GW signals can be identified from the spatial correlations encoded in the times-of-arrival of widely spaced pulsar-pairs. The Chinese Pulsar Timing Array (CPTA) is a collaboration aiming at the direct GW detection with observations carried out using Chinese radio telescopes. This short article serves as a `table of contents' for a forthcoming series of papers related to the CPTA Data Release 1 (CPTA DR1) which uses observations from the Five-hundred-meter Aperture Spherical radio Telescope (FAST). Here, after summarizing the time span and accuracy of CPTA DR1, we report the key results of our statistical inference finding a correlated signal with amplitude \log A_{\rm c}= -14.4 \,^{+1.0}_{-2.8} for spectral index in the range of $\alpha\in [-1.8, 1.5]$ assuming a GW background (GWB) induced quadrupolar correlation. The search for the Hellings-Downs (HD) correlation curve is also presented, where some evidence for the HD correlation has been found that a 4.6-$\sigma$ statistical significance is achieved using the discrete frequency method around the frequency of 14 nHz. We expect that the future International Pulsar Timing Array data analysis and the next CPTA data release will be more sensitive to the nHz GWB, which could verify the current results.Comment: 18 pages, 6 figures, submitted to "Research in astronomy and astrophysics" 22nd March 202