A semi-quantitative upconversion nanoparticle-based immunochromatographic assay for SARS-CoV-2 antigen detection

The unprecedented public health and economic impact of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been met with an equally unprecedented scientific response. Sensitive point-of-care methods to detect SARS-CoV-2 antigens in clinical specimens are urgently required for the rapid screening of individuals with viral infection. Here, we developed an upconversion nanoparticle-based lateral flow immunochromatographic assay (UCNP-LFIA) for the high-sensitivity detection of SARS-CoV-2 nucleocapsid (N) protein. A pair of rabbit SARS-CoV-2 N-specific monoclonal antibodies was conjugated to UCNPs, and the prepared UCNPs were then deposited into the LFIA test strips for detecting and capturing the N protein. Under the test conditions, the limit of detection (LOD) of UCNP-LFIA for the N protein was 3.59 pg/mL, with a linear range of 0.01–100 ng/mL. Compared with that of the current colloidal gold-based LFIA strips, the LOD of the UCNP-LFIA-based method was increased by 100-fold. The antigen recovery rate of the developed method in the simulated pharyngeal swab samples ranged from 91.1 to 117.3%. Furthermore, compared with the reverse transcription-polymerase chain reaction, the developed UCNP-LFIA method showed a sensitivity of 94.73% for 19 patients with COVID-19. Thus, the newly established platform could serve as a promising and convenient fluorescent immunological sensing approach for the efficient screening and diagnosis of COVID-19

Genome-Wide Analysis of DNA Methylation and Cigarette Smoking in a Chinese Population

Background: Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited. Objectives: We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population. Methods: We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes. Results: We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking. Conclusion: We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation. Citation: Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966–973; http://dx.doi.org/10.1289/ehp.150983

A Vital Signs Fast Detection and Extraction Method of UWB Impulse Radar Based on SVD

The identification of weak vital signs has always been one of the difficulties in the field of life detection. In this paper, a novel vital sign detection and extraction method with high efficiency, high precision, high sensitivity and high signal-to-noise ratio is proposed. Based on the NVA6100 pulse radar system, the radar matrix which contains several radar pulse detection signals is received. According to the characteristics of vital signs and radar matrices, the Singular Value Decomposition (SVD) is adopted to perform signal denoising and decomposition after preprocessing, and the temporal and spatial eigenvectors of each principal component are obtained. Through the energy proportion screening, the Wavelet Transform decomposition and linear trend suppression, relatively pure vital signs in each principal component, are obtained. The human location is detected by the Energy Entropy of spatial eigenvectors, and the respiratory signal and heartbeat signal are restored through a Butterworth Filter and an MTI harmonic canceller. Finally, through an analysis of the performance of the algorithm, it is proved to have the properties of efficiency and accuracy

CircZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and its translation function

Abstract Background Pulmonary fibrosis is a growing clinical problem that develops as a result of abnormal wound healing, leading to breathlessness, pulmonary dysfunction and ultimately death. However, therapeutic options for pulmonary fibrosis are limited because the underlying pathogenesis remains incompletely understood. Circular RNAs, as key regulators in various diseases, remain poorly understood in pulmonary fibrosis induced by silica. Methods We performed studies with fibroblast cell lines and silica-induced mouse pulmonary fibrosis models. The expression of circZNF609, miR-145-5p, and KLF4 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RNA immunoprecipitation (RIP) assays and m6A RNA immunoprecipitation assays (MeRIP), Western blotting, immunofluorescence assays, and CCK8 were performed to investigate the role of the circZNF609/miR-145-5p/KLF4 axis and circZNF609-encoded peptides in fibroblast activation. Results Our data showed that circZNF609 was downregulated in activated fibroblasts and silica-induced fibrotic mouse lung tissues. Overexpression of circZNF609 could inhibit fibroblast activation induced by transforming growth factor-β1 (TGF-β1). Mechanically, we revealed that circZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and circZNF609-encoded peptides. Furthermore, circZNF609 was highly methylated and its expression was controlled by N6-methyladenosine (m6A) modification. Lastly, in vivo studies revealed that overexpression of circZNF609 attenuates silica-induced lung fibrosis in mice. Conclusions Our data indicate that circZNF609 is a critical regulator of fibroblast activation and silica-induced lung fibrosis. The circZNF609 and its derived peptides may represent novel promising targets for the treatment of pulmonary fibrosis

Subtle distinction in molecular structure of flavonoids leads to vastly different coating efficiency and mechanism of metal-polyphenol networks with excellent antioxidant activities

Metal-polyphenol networks (MPNs) are of immense scientific interest because of their simple and rapid process to deposit on various substrates or particles with different shapes. However, there are rare reports on the effect of polyphenol molecular structure on coating efficiency and mechanism of MPNs. Herein, three typical flavonoid polyphenols, catechin (Cat), epigallocatechin (EGC) and procyanidin (PC), with the same skeleton (C6-C3-C6) but subtle distinction in molecular structure, were selected to build MPN coatings with ferric ions (Fe3+). And various techniques combined with the density functional theory (DFT) were applied to deeply reveal the roles of coordinative phenolic hydroxyl groups as well as noncovalent interactions (hydrogen bonding and π − π stacking) in the formation of flavonoid-based MPNs. We found that more accessible numbers of coordinative phenolic hydroxyl groups, the higher coating efficiency. In these flavonoid-based MPNs, the single-complex is the predominant during the coordinative modes between phenolic hydroxyl and Fe3+, not the previously reported mono-complex, bis-complex and/or tris-complex. Besides coordinative interaction, noncovalent interactions also contribute to MPNs formation, and hydrogen bonds prevail in the noncovalent interaction compared with π-π stacking. And these engineered MPN coatings can endow the substrate with excellent antioxidant activities. This study contributes to in-depth understanding the building mechanism of flavonoid-based MPNs, and increasing coating efficiency by choosing proper polyphenols

Quantitative proteomics reveals the crucial role of YbgC for Salmonella enterica serovar Enteritidis survival in egg white

Salmonella enterica serovar Enteritidis (S. Enteritidis) is a food-borne bacterial pathogen that can cause human salmonellosis predominately by contamination of eggs and egg products. However, its survival mechanisms in egg white are not fully understood, especially from a proteomic point of view. In this study, the proteomic profiles of S. Enteritidis in Luria-Bertani (LB) broth containing 50% and 80% egg white, and in whole egg white were compared with the profile in LB broth using iTRAQ technology to identify key proteins that were involved in S. Enteritidis survival in egg white. It was found that there were 303, 284 and 273 differentially expressed proteins in S. Enteritidis after 6 h exposure to whole, 80% and 50% egg white, respectively. Most of up-regulated proteins were primarily associated with iron acquisition, cofactor and amino acid biosynthesis, transporter, regulation and stress responses, whereas down-regulated proteins were mainly involved in energy metabolism, virulence as well as motility and chemotaxis. Three stress response-related proteins (YbgC, TolQ, TolA) of the tol-pal system responsible for maintaining cell membrane stability of Gram-negative bacteria were up-regulated in S. Enteritidis in response to whole egg white. Interestingly, deletion of ybgC resulted in a decreased resistance of S. Enteritidis to egg white. Compared with the wild type and complementary strains, a 3-log population reduction was observed in △ybgC mutant strain after incubation in whole egg white for 24 h. Cellular morphology of △ybgC mutant strain was altered from rods to spheres along with cell lysis in whole egg white. Furthermore, deletion of ybgC decreased the expression of tol-pal system-related genes (tolR, tolA). Collectively, these proteomic and mutagenic analysis reveal that YbgC is essential for S. Enteritidis survival in egg white.</p

Substitution of Nonpharmacologic Therapy With Opioid Prescribing for Pain During the COVID-19 Pandemic

Importance: During the pandemic, access to medical care unrelated to COVID-19 was limited because of concerns about viral spread and corresponding policies. It is critical to assess how these conditions affected modes of pain treatment, given the addiction risks of prescription opioids. Objective: To assess the trends in opioid prescription and nonpharmacologic therapy (ie, physical therapy and complementary medicine) for pain management during the COVID-19 pandemic in 2020 compared with the patterns in 2019. Design, setting, and participants: This retrospective, cross-sectional study used weekly claims data from 24 million US patients in a nationwide commercial insurance database (Optum's deidentified Clinformatics Data Mart Database) from January 1, 2019, to September 31, 2020. Among patients with diagnoses of limb, extremity, or joint pain, back pain, and neck pain for each week, patterns of treatment use were identified and evaluated. Data analysis was performed from April 1, 2021, to September 31, 2021. Main outcomes and measures: The main outcomes of interest were weekly rates of opioid prescriptions, the strength and duration of related opioid prescriptions, and the use of nonpharmacologic therapy. Transition rates between different treatment options before the outbreak and during the early months of the pandemic were also assessed. Results: A total of 21 430 339 patients (mean [SD] age, 48.6 [24.0] years; 10 960 507 [51.1%] female; 909 061 [4.2%] Asian, 1 688 690 [7.9%] Black, 2 276 075 [10.6%] Hispanic, 11 192 789 [52.2%] White, and 5 363 724 [25.0%] unknown) were enrolled during the first 3 quarters in 2019 and 20 759 788 (mean [SD] age, 47.0 [23.8] years; 10 695 690 [51.5%] female; 798 037 [3.8%] Asian; 1 508 023 [7.3%] Black, 1 976 248 [9.5%] Hispanic, 10 059 597 [48.5%] White, and 6 417 883 [30.9%] unknown) in the first 3 quarters of 2020. During the COVID-19 pandemic, the proportion of patients receiving a pain diagnosis was smaller than that for the same period in 2019 (mean difference, -15.9%; 95% CI, -16.1% to -15.8%). Patients with pain were more likely to receive opioids (mean difference, 3.5%; 95% CI, 3.3%-3.7%) and less likely to receive nonpharmacologic therapy (mean difference, -6.0%; 95% CI, -6.3% to -5.8%), and opioid prescriptions were longer and more potent during the early pandemic in 2020 relative to 2019 (mean difference, 1.07 days; 95% CI, 1.02-1.17 days; mean difference, 0.96 morphine milligram equivalents; 95% CI, 0.76-1.20). Analysis of individuals' transitions between treatment options for pain found that patients were more likely to transition out of nonpharmacologic therapy, replacing it with opioid prescriptions for pain management during the COVID-19 pandemic than in the year before. Conclusions and relevance: Nonpharmacologic therapy is a benign treatment for pain often recommended instead of opioid therapy. The decrease in nonpharmacologic therapy and increase in opioid prescription during the COVID-19 pandemic found in this cross-sectional study, especially given longer days of prescription and more potent doses, may exacerbate the US opioid epidemic. These findings suggest that it is imperative to investigate the implications of limited medical access on treatment substitution, which may increase patient risk, and implement policies and guidelines to prevent those substitutions