Background The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. Methods The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. Results The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). Conclusions The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.
Senescent cells (SCs) accumulate with age and after genotoxic stress, such as total-body irradiation (TBI)1–6. Clearance of SCs in a progeroid mouse model using a transgenic approach delays several age-associated disorders7, suggesting that SCs play a causative role in certain age-related pathologies. Thus, a ‘senolytic’ pharmacological agent that can selectively kill SCs holds promise for rejuvenating tissue stem cells and extending health span. To test this idea, we screened a collection of compounds and identified ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL-2 and BCL-xL) as a potent senolytic drug. We show that ABT263 selectively kills SCs in culture in a cell type– and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells. Thus, senolytic drugs may represent a new class of radiation mitigators and anti-aging agents.
MEG3 is a maternally expressed imprinted gene suggested to function as a non-coding RNA. Our previous studies suggest that MEG3 has a function of tumor suppression. The tumor suppressor p53 plays a central role in tumor suppression and mediates the functions of many other tumor suppressors. Therefore, we hypothesized that MEG3 functions through activation of p53. We found that transfection of expression constructs for MEG3 and its isoforms results in a significant increase in p53 protein levels and dramatically stimulates p53-dependent transcription from a p53-responsive promoter. Using this as the functional assay, we demonstrated that the open reading frames encoded by MEG3 transcripts are not required for MEG3 function, and the folding of MEG3 RNA is critical to its function, supporting the concept that MEG3 functions as a non-coding RNA. We further found that MEG3 stimulates expression of the growth differentiation factor 15 (GDF15) by enhancing p53 binding to the GDF15 gene promoter. Interestingly, MEG3 does not stimulate p21 CIP1 expression, suggesting that MEG3 can regulate the specificity of p53 transcriptional activation. p53 degradation is mainly mediated by the mouse double minute 2 homolog (MDM2). We found that MDM2 levels were down-regulated in cells transfected with MEG3, suggesting that MDM2 suppression contributes at least in part to p53 accumulation induced by MEG3. Finally, we found that MEG3 is able to inhibit cell proliferation in the absence of p53. These data suggest that MEG3 non-coding RNA may function as a tumor suppressor, whose action is mediated by both p53-dependent and p53-independent pathways.
Layer number and stacking order of few‐layer graphene (FLG) are of particular interest since they directly determine the performance of graphene‐based electronic devices. By analyzing Raman spectra and Raman images, quantitative indices are extracted to discriminate the thickness of AB‐stacked FLG from single‐ to five‐layer graphene; a few key spectral characteristics are also identified for FLG with misoriented stacking.
This work addresses a novel and challenging problem of estimating the full 3D hand shape and pose from a single RGB image. Most current methods in 3D hand analysis from monocular RGB images only focus on estimating the 3D locations of hand keypoints, which cannot fully express the 3D shape of hand. In contrast, we propose a Graph Convolutional Neural Network (Graph CNN) based method to reconstruct a full 3D mesh of hand surface that contains richer information of both 3D hand shape and pose. To train networks with full supervision, we create a large-scale synthetic dataset containing both ground truth 3D meshes and 3D poses. When fine-tuning the networks on real-world datasets without 3D ground truth, we propose a weakly-supervised approach by leveraging the depth map as a weak supervision in training. Through extensive evaluations on our proposed new datasets and two public datasets, we show that our proposed method can produce accurate and reasonable 3D hand mesh, and can achieve superior 3D hand pose estimation accuracy when compared with state-of-the-art methods.
Contact angle goniometry is conducted for epitaxial graphene on SiC. Although only a single layer of epitaxial graphene exists on SiC, the contact angle drastically changes from 69 degrees on SiC substrates to 92 degrees on graphene. It is found that there is no thickness dependence of the contact angle from the measurements of single-, bi-, and multilayer graphene and highly ordered pyrolytic graphite (HOPG). After graphene is treated with oxygen plasma, the level of damage is investigated by Raman spectroscopy and the correlation between the level of disorder and wettability is reported. By using a low-power oxygen plasma treatment, the wettability of graphene is improved without additional damage, which can solve the adhesion issues involved in the fabrication of graphene devices.
ObjectiveTo examine whether gender differences in primary care consultation rates (1) vary by age and deprivation status and (2) diminish when consultation for reproductive reasons or common underlying morbidities are accounted for.DesignCross-sectional study of a cohort of patients registered with general practice.SettingUK primary care.SubjectsPatients (1 869 149 men and 1 916 898 women) registered with 446 eligible practices in 2010.Primary outcome measuresPrimary care consultation rate.ResultsThis study analyses routinely collected primary care consultation data. The crude consultation rate was 32% lower in men than women. The magnitude of gender difference varied across the life course, and there was no ‘excess’ female consulting in early and later life. The greatest gender gap in primary care consultations was seen among those aged between 16 and 60 years. Gender differences in consulting were higher in people from more deprived areas than among those from more affluent areas. Accounting for reproductive-related consultations diminished but did not eradicate the gender gap. However, consultation rates in men and women who had comparable underlying morbidities (as assessed by receipt of medication) were similar; men in receipt of antidepressant medication were only 8% less likely to consult than women in receipt of antidepressant medication (relative risk (RR) 0.916, 95% CI 0.913 to 0.918), and men in receipt of medication to treat cardiovascular disease were just 5% less likely to consult (RR=0.950, 95% CI 0.948 to 0.952) than women receiving similar medication. These small gender differences diminished further, particularly for depression (RR=0.950, 95% CI 0.947 to 0.953), after also taking account of reproductive consultations.ConclusionsOverall gender differences in consulting are most marked between the ages of 16 and 60 years; these differences are only partially accounted for by consultations for reproductive reasons. Differences in consultation rates between men and women were largely eradicated when comparing men and women in receipt of medication for similar underlying morbidities.
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