Detection of asymptomatic or subclinical novel human coronavirus SARS-CoV-2 infection is critical for understanding the overall prevalence and infection potential of COVID-19. To estimate the ...cumulative prevalence of SARS-CoV-2 infection in China, we evaluated the host serologic response, measured by the levels of immunoglobulins M and G in 17,368 individuals, in the city of Wuhan, the epicenter of the COVID-19 pandemic in China, and geographic regions in the country, during the period from 9 March 2020 to 10 April 2020. In our cohorts, the seropositivity in Wuhan varied between 3.2% and 3.8% in different subcohorts. Seroposivity progressively decreased in other cities as the distance to the epicenter increased. Patients who visited a hospital for maintenance hemodialysis and healthcare workers also had a higher seroprevalence of 3.3% (51 of 1,542, 2.5-4.3%, 95% confidence interval (CI)) and 1.8% (81 of 4,384, 1.5-2.3%, 95% CI), respectively. More studies are needed to determine whether these results are generalizable to other populations and geographic locations, as well as to determine at what rate seroprevalence is increasing with the progress of the COVID-19 pandemic. Serologic surveillance has the potential to provide a more faithful cumulative viral attack rate for the first season of this novel SARS-CoV-2 infection.
An ongoing outbreak of severe respiratory pneumonia associated with the 2019 novel coronavirus has recently emerged in China. Here we report the epidemiological, clinical, laboratory and radiological ...characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test results from different samples including oropharyngeal swab, blood, urine and stool with 3 different fluorescent RT-PCR kits. Nine out of the 19 patients had 2019-nCoV infection detected using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. These three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the computed tomography scans and nucleic acid detection.
High myopia is a leading cause of blindness worldwide. Myopia progression may lead to pathological changes of lens and affect the outcome of lens surgery, but the underlying mechanism remains ...unclear. Here, we find an increased lens size in highly myopic eyes associated with up-regulation of β/γ-crystallin expressions. Similar findings are replicated in two independent mouse models of high myopia. Mechanistic studies show that the transcription factor MAF plays an essential role in up-regulating β/γ-crystallins in high myopia, by direct activation of the crystallin gene promoters and by activation of TGF-β1-Smad signaling. Our results establish lens morphological and molecular changes as a characteristic feature of high myopia, and point to the dysregulation of the MAF-TGF-β1-crystallin axis as an underlying mechanism, providing an insight for therapeutic interventions.
The development of an accurate and efficient method for detecting missing bolts in engineering structures is crucial. To this end, a missing bolt detection method that leveraged machine vision and ...deep learning was developed. First, a comprehensive dataset of bolt images captured under natural conditions was constructed, which improved the generality and recognition accuracy of the trained bolt target detection model. Second, three deep learning network models, namely, YOLOv4, YOLOv5s, and YOLOXs, were compared, and YOLOv5s was selected as the bolt target detection model. With YOLOv5s as the target recognition model, the bolt head and bolt nut had average precisions of 0.93 and 0.903, respectively. Third, a missing bolt detection method based on perspective transformation and IoU was presented and validated under laboratory conditions. Finally, the proposed method was applied to an actual footbridge structure to test its feasibility and effectiveness in real engineering scenarios. The experimental results showed that the proposed method could accurately identify bolt targets with a confidence level of over 80% and detect missing bolts under different image distances, perspective angles, light intensities, and image resolutions. Moreover, the experimental results on a footbridge demonstrated that the proposed method could reliably detect the missing bolt even at a shooting distance of 1 m. The proposed method provided a low-cost, efficient, and automated technical solution for the safety management of bolted connection components in engineering structures.
This paper aims to provide an investigation of the bulge deformation rules by using finite element analysis software, ABAQUS/Standard. A three-dimensional thermo-mechanical coupling model, ...considering the dynamic contact between the slab and rolls, has been established to study the temperature and bulge deformation distributions of the slab over the casting process. The simulated results of temperature profile were compared with the measured temperatures during the continuous casting process, the results of which showed a high agreement. Moreover, the bulge deformation rules of the slab were investigated systematically, especially at the thickness direction of the cross section which is the bulge deformation of the slab on the narrow side. A wave motion was found in the bulge deformation on the wide side of the slab cross section due to the joint effect of the ferrostatic pressure and the roller supporting force. The bulge deformation on the narrow side without the constraint from the roller support was cumulative, which was greater than the recovery count and compensated the bulge deformation on the wide side. In addition, the influences of various casting process parameters on bulge deformation were studied systematically in this paper. The results showed that bulge deformation on the narrow side and the wide side both increased with an increase in casting speeds and roll pitch. The method of fixed-gap and variable-diameter was suggested to be applied in the manufacture process in order to reduce the bulge deformation.
The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the ...disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.
The Frizzleds (FZDs) receptors on the cell surface belong to the class F of G protein-coupled receptors (GPCRs) which are the major receptors of WNT protein that mediates the classical WNT signaling ...pathway and other non-classical pathways. Besides, the FZDs also play a core role in tissue regeneration and tumor occurrence. With the structure and mechanism of FZDs activation becoming clearer, a series of FZDs modulators (inhibitors and agonists) have been developed, with the hope of bringing benefits to the treatment of cancer and degenerative diseases. Most of the FZDs inhibitors (small molecules, antibodies or designed protein inhibitors) block WNT signaling through binding to the cysteine-rich domain (CRD) of FZDs. Several small molecules impede FZDs activation by targeting to the third intracellular domain or the transmembrane domain of FZDs. However, three small molecules (FZM1.8, SAG1.3 and purmorphamine) activate the FZDs through direct interaction with the transmembrane domain. Another type of FZDs agonists are bivalent or tetravalent antibodies which activate the WNT signaling via inducing FZD-LRP5/6 heterodimerization. In this article, we reviewed the FZDs modulators reported in recent years, summarized the critical molecules’ discovery processes and the elucidated relevant structural and pharmacological mechanisms. We believe the summaried molecular mechanisms of the relevant modulators could provide important guidance and reference for the future development of FZD modulators.
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Inflammation and elevated expression of high temperature requirement A serine peptidase 1 (HTRA1) are known high risk factors for age-related macular degeneration (AMD). However, the specific ...mechanism that HTRA1 causes AMD and the relationship between HTRA1 and inflammation remains unclear. We found that lipopolysaccharide (LPS) induced inflammation enhanced the expression of HTRA1, NF-κB, and p-p65 in ARPE-19 cells. Overexpression of HTRA1 up-regulated NF-κB expression, and on the other hand knockdown of HTRA1 down-regulated the expression of NF-κB. Moreover, NF-κB siRNA has no significant effect on the expression of HTRA1, suggesting HTRA1 works upstream of NF-κB. These results demonstrated that HTRA1 plays a pivotal role in inflammation, explaining possible mechanism of overexpressed HTRA1-induced AMD. Celastrol, a very common anti-inflammatory and antioxidant drug, was found to suppress inflammation by inhibiting phosphorylation of p65 protein efficaciously in RPE cells, which may be applied to the therapy of age-related macular degeneration.