Coronavirus disease 2019 (COVID‐19) is a respiratory disorder caused by the highly contagious severe acute respiratory syndrome coronavirus 2. The immunopathological characteristics of patients with ...COVID‐19, either systemic or local, have not been thoroughly studied. In the present study, we analysed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID‐19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells and natural killer cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID‐19. Interleukin‐6 (IL‐6), IL‐10 and C‐reactive protein were remarkably up‐regulated in patients with severe COVID‐19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL‐6, IL‐10 and C‐reactive protein are reliable indicators of severe COVID‐19.
COVID‐19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells and natural killer cells. Interleukin‐6 (IL‐6), IL‐10 and C‐reactive protein were remarkably up‐regulated in patients with severe COVID‐19. IL‐6, IL‐10 and C‐reactive protein are reliable indicators of severe COVID‐19.
Generation of induced pluripotent stem cells typically requires the ectopic expression of transcription factors to reactivate the pluripotency network. However, it remains largely unclear what ...remodeling events on endogenous chromatin trigger reprogramming toward induced pluripotent stem cells (iPSCs). Toward this end, we employed CRISPR activation to precisely target and remodel endogenous gene loci of Oct4 and Sox2. Interestingly, we found that single-locus targeting of Sox2 was sufficient to remodel and activate Sox2, which was followed by the induction of other pluripotent genes and establishment of the pluripotency network. Simultaneous remodeling of the Oct4 promoter and enhancer also triggered reprogramming. Authentic pluripotent cell lines were established in both cases. Finally, we showed that targeted manipulation of histone acetylation at the Oct4 gene locus could also initiate reprogramming. Our study generated authentic iPSCs with CRISPR activation through precise epigenetic remodeling of endogenous loci and shed light on how targeted chromatin remodeling triggers pluripotency induction.
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•Endogenous Oct4 and Sox2 can be targeted and activated by CRISPR activation•Activation of endogenous Oct4 or Sox2 triggers reprogramming to pluripotency•Oct4 promoter and enhancer are simultaneously remodeled by dCas9-SunTag-p300core•Authentic induced pluripotent stem cells are generated with CRISPR activation
Ding and colleagues demonstrate that induced pluripotency can be achieved through targeted activation of endogenous Oct4 or Sox2 genes. With CRISPR activation, the promoter and enhancer are specifically remodeled, Oct4 or Sox2 is derepressed in fibroblasts, and reprogramming is triggered toward pluripotency.
Low detection and nonadherence are major problems in current management approaches for patients with suspected atrial fibrillation (AF). Mobile health devices may enable earlier AF detection and ...improved AF management.
This study sought to investigate the effectiveness of AF screening in a large population-based cohort using smart device–based photoplethysmography (PPG) technology, combined with a clinical care AF management pathway using a mobile health approach.
AF screening was performed with smart devices using PPG technology, which were made available for the population ≥18 years of age across China. Monitoring for at least 14 days with a wristband (Honor Band 4) or wristwatch (Huawei Watch GT, Honor Watch, Huawei Technologies Co., Ltd., Shenzhen, China) was allowed. The patients with “possible AF” episodes using the PPG algorithm were further confirmed by health providers among the MAFA (mobile AF app) Telecare center and network hospitals, with clinical evaluation, electrocardiogram, or 24-h Holter monitoring.
There were 246,541 individuals who downloaded the PPG screening app, and 187,912 individuals used smart devices to monitor their pulse rhythm between October 26, 2018, and May 20, 2019. Among those with PPG monitoring (mean age 35 years, 86.7% male), 424 (of 187,912, 0.23%) (mean age 54 years, 87.0% male) received a “suspected AF” notification. Of those effectively followed up, 227 individuals (of 262, 87.0%) were confirmed as having AF, with the positive predictive value of PPG signals being 91.6% (95% confidential interval CI: 91.5% to 91.8%). Both suspected AF and identified AF markedly increased with age (p for trend <0.001), and individuals in Northeast China had the highest proportion of detected AF of 0.28% (95% CI: 0.20% to 0.39%). Of the individuals with identified AF, 216 (of 227, 95.1%) subsequently entered a program of integrated AF management using a mobile AF application; approximately 80% of high-risk patients were successfully anticoagulated.
Based on the present study, continuous home monitoring with smart device–based PPG technology could be a feasible approach for AF screening. This would help efforts at screening and detection of AF, as well as early interventions to reduce stroke and other AF-related complications. (Mobile Health mHealth Technology for Improved Screening, Patient Involvement and Optimizing Integrated Care in Atrial Fibrillation MAFA II; ChiCTR-OOC-17014138)
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The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or ...pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.
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•PAC-MAN is a CRISPR-based strategy for RNA-guided viral RNA inhibition and degradation•Cas13d PAC-MAC is effective at targeting and cleaving SARS-CoV-2 sequences•Cas13d PAC-MAC can reduce H1N1 IAV load in respiratory epithelial cells•A group of six crRNAs can target more than 90% of all coronaviruses
A CRISPR-based strategy is developed to target conserved sequences across coronaviruses and other pathogenic viruses.
Summary Background & aims The results of human clinical trials that have investigated the effects of resveratrol on blood pressure are inconsistent. We aimed to quantitatively evaluate the effects of ...resveratrol on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Methods We conducted a strategic literature search of PubMed, EMBASE, MEDLINE, and the Cochrane Library (updated to January, 2014) for randomized controlled trials that evaluate the effects of resveratrol on SBP and DBP. Study quality was assessed using the Jadad scale. Weighted mean differences were calculated for net changes in SBP and DBP using fixed-effects or random-effects models. We performed pre-specified subgroup, sensitivity and meta-regression analyses to evaluate potential the heterogeneity. Dose effects of resveratrol on SBP and DBP were estimated using meta-regression analyses. Results Six studies comprising a total of 247 subjects were included in our meta-analysis. The overall outcome of the meta-analysis indicates that resveratrol consumption can not significantly reduce SBP and DBP. Subgroup analyses indicated that higher-dose of resveratrol consumption (≥150 mg/d) significantly reduces SBP of −11.90 mmHg (95% CI: −20.99, −2.81 mmHg, P = 0.01), whereas lower dose of resveratrol did not show a significant lowering effect on SBP. The meta-regression analyses did not indicate dose effects of resveratrol on SBP or DBP. Conclusions The present meta-analysis indicates that resveratrol consumption significantly decreases the SBP level at the higher dose, while resveratrol has no significant effects on DBP levels. Additional high-quality studies are needed to further evaluate the causal conclusions.
We report a robust, versatile approach called CRISPR live-cell fluorescent in situ hybridization (LiveFISH) using fluorescent oligonucleotides for genome tracking in a broad range of cell types, ...including primary cells. An intrinsic stability switch of CRISPR guide RNAs enables LiveFISH to accurately detect chromosomal disorders such as Patau syndrome in prenatal amniotic fluid cells and track multiple loci in human T lymphocytes. In addition, LiveFISH tracks the real-time movement of DNA double-strand breaks induced by CRISPR-Cas9-mediated editing and consequent chromosome translocations. Finally, by combining Cas9 and Cas13 systems, LiveFISH allows for simultaneous visualization of genomic DNA and RNA transcripts in living cells. The LiveFISH approach enables real-time live imaging of DNA and RNA during genome editing, transcription, and rearrangements in single cells.
•Three-dimensional graphene foam was synthesized by plasma-enhanced CVD.•The graphene foam exhibited a high electrical conductivity of 125S/cm.•The graphene foam showed a large surface area of ...625.4cm2/g.•The prepared graphene foam/epoxy composites showed a high conductivity.•The derived graphene oxide foam showed an excellent absorption capability.
A three-dimensional (3D), free-standing graphene foam was prepared by plasma-enhanced chemical vapor deposition on nickel-foam. The prepared graphene foam was found to consist of few-layered vertically-aligned graphene sheets with highly graphite structure. Owing to the 3D interconnected porous nanostructures, the graphene foam exhibited a high electrical conductivity of 125S/cm and a large surface area of 625.4cm2/g. For practical application, we prepared the graphene foam/epoxy composites showing a maximum conductivity of 196S/m at 2.5vol.% filler loading, and a rather low percolation threshold of 0.18vol.%. Furthermore, the derived graphene oxide foam exhibited an excellent absorption capability (177.6mg/g for As(V), 399.3mg/g for Pb(II)) and recyclability (above 90% removal efficiency after five cycles) for the removal of heavy metal ions. The present study reveals that the multifunctional graphene foam may broaden the graphene-based materials for the applications in electrically conductive composites and environmental cleanup.
Herein, we present new design principles for gain enhancement and cross-polarization suppression in dual-polarized cavity-backed antennas and demonstrate the capability in an octagonal cavity-backed ...open prism antenna (OCROP). In our approach, the gain is enhanced through an optimal flaring procedure and a novel metallic iris is used to control the electromagnetic fields and thereby reduce the cross-polarization. Previously, we investigated a dual-polarized OCROP antenna configuration and were able to simultaneously achieve 50% impedance bandwidth, 40% cross-polarization bandwidth (≤25 dB), and 10.2 dBi peak gain. In this study, we investigated gain enhancement by flaring an upper section of the ground cavity sidewalls, while maintaining a constant cavity height. Two cases were investigated: (1) the flare angle was modified, while the ratio of the non-flared to flared sidewall heights was kept constant, and (2) the ratio of the non-flared to flared sidewall heights was varied. In case 1, we established that, while increasing the flare angle results in a gain increase, there is a limit, as cross-polarization at the upper operating frequencies increases. In case 2, we were able to reduce the aperture phase error and achieve a higher peak gain of 12.8 dBi. To address the increased cross-polarization at the high frequency end when a large flare was used, we added a metallic iris at the junction of non-flared and flared sidewalls. We showed that increasing the iris width generally decreases the cross-polarization at high frequencies, without compromising the gain and impedance bandwidth. At an optimal width, it provides a nearly constant, low cross-polarization (below -25.8 dB) and a peak gain of 13.3 dBi, across the entire 50.7% impedance bandwidth of the antenna. We fabricated and successfully tested a prototype to verify the design and simulation approach. These results prove that incorporating an aperture flare with a metallic iris can significantly improve the gain and cross-polarization performance of cavity-backed antennas.
Simultaneously enhancing multiple antenna performance parameters is a demanding task, especially with a challenging set of design goals. In this paper, by carefully deriving a compatible set of ...enhancement techniques, we propose a compact/lightweight/low-cost high-performance L-band octagonal cavity-backed hybrid antenna with multiple attractive features: dual-polarization, wide impedance bandwidth, low cross-polarization, high gain, and high aperture efficiency. The ground cavity is octagonal, which allows the antenna to have a small footprint, and, more importantly, low cross-polarization and high aperture efficiencies when compared to a commonly-used square design. The hybrid design relies on the resonance merging of two radiating elements, i.e., radiating feedlines and a conductive open prism, to form a wide impedance bandwidth. To permit polarization diversity and low cross-polarization, it is differentially and orthogonally fed. Herein, a series of parametric simulation studies on antenna configurations provide information on how to improve the impedance bandwidth and cross-polarization performance. To verify the simulation studies, an antenna prototype was fabricated and tested. Excellent agreement between the simulated and measured results was reached.
This paper investigates the miniaturization capability of split ring array antennas embedded in a low-permittivity dielectric substrate, in comparison with the same-sized high-permittivity dielectric ...resonator antennas (DRAs). In order to understand the miniaturization performance, a size-fixed dielectric substrate with different split ring arrays is studied. The simulation results show that the miniaturization capability increases with decreased unit cell resonant frequency and/or increased unit cell induced permeability. Miniaturizations as high as 25.54 times that of a high-permittivity DRA are obtained with split rings, etched on a dielectric substrate having a low permittivity of 2.2. Furthermore, this excessive miniaturization does not come at the expense of excessive deterioration of the antenna impedance bandwidth, gain, and radiation efficiency. Consequently, the miniaturized split ring arrays still provide high gains over wider bandwidths. This inference is further verified by comparing the miniaturization and other antenna performance parameters with three other modified split ring configurations. To experimentally verify this work, a split ring antenna was fabricated and tested, and good agreement between the simulated and measured results was observed. The results of this study indicate that adding resonant metallic inclusions into low- permittivity DRAs significantly increases their miniaturization capability, without overly deteriorating the performance.
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