LncRNA PART1 Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating TFAP2C/DUSP5 Axis via miR-302a-3p.

BACKGROUND AND OBJECTIVES: Myocardial ischemia-reperfusion injury (MIRI) refers to the damage of cardiac function caused by restoration of blood flow perfusion in ischemic myocardium. However, long non-coding RNA prostate androgen regulated transcript 1 (PART1)'s role in MIRI remain unclear. METHODS: Immunofluorescence detected LC3 expression. Intermolecular relationships were verified by dual luciferase reporter assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and transferase-mediated dUTP nick-end labeling (TUNEL) assays analyzed cell viability and apoptosis. The release of lactate dehydrogenase was tested via enzyme-linked immunosorbent assay (ELISA). Left anterior descending coronary artery surgery induced a MIRI mouse model. Infarct area was detected by 2,3,5-triphenyltetrazolium chloride staining. Hematoxylin and eosin staining examined myocardial injury. ELISA evaluated myocardial marker (creatine kinase MB) level. RESULTS: PART1 was decreased in hypoxia/reoxygenation (H/R) induced AC16 cells and MIRI mice. PART1 upregulation attenuated the increased levels of Bax, beclin-1 and the ratio of LC3II/I, and enhanced the decrease of Bcl-2 and p62 expression in H/R-treated cells. PART1 upregulation alleviated H/R-triggered autophagy and apoptosis via miR-302a-3p. Mechanically, PART1 targeted miR-302a-3p to upregulate transcription factor activating enhancer-binding protein 2C (TFAP2C). TFAP2C silencing reversed the protected effects of miR-302a-3p inhibitor on H/R treated AC16 cells. We further established TFAP2C combined to dual-specificity phosphatase 5 (DUSP5) promoter and activated DUSP5. TFAP2C upregulation suppressed H/R-stimulated autophagy and apoptosis through upregulating DUSP5. Overexpressed PART1 reduced myocardial infarction area and attenuated MIRI in mice. CONCLUSION: PART1 improved the autophagy and apoptosis in H/R-exposed AC16 cells through miR-302a-3p/TFAP2C/DUSP5 axis, which might provide novel targets for MIRI treatment.

Effect of YuPingFeng granules on clinical symptoms of stable COPD: study protocol for a multicenter, double-blind, and randomized controlled trial.

BACKGROUND: Reducing current clinical symptoms and the risks of future exacerbations is the main goal of stable COPD management. Traditional Chinese medicine has unique advantages in chronic disease management. YuPingFeng (YPF), as a classical prescription, has been proven to reduce the risk of exacerbations, but there is a lack of high-quality evidence for the assessment of clinical symptoms and quality of life, particularly for the assessment of treatment response of microecology and immunity. METHODS/DESIGN: This is a prospective, multicentre, randomized, double-blind, placebo-controlled clinical trial. A total of 316 eligible subjects with moderate to severe COPD will be randomized 1:1 to receive YPF or placebo. Participants will receive either YPF or a placebo at 5 g three times daily for 52 weeks. The primary outcome will be the change in the COPD Assessment Test (CAT) score after 52 weeks of treatment. Secondary outcomes will include changes in the St George's Respiratory Questionnaire (SGRQ) score and clinical symptom score, among others. Outcomes will be measured at each visit. The study will continue for 52 weeks and will include six visits to each subject (at day 0 and weeks 4,12,24,36 and 52). In the event of exacerbations, subjects will be required to go back to the hospital once on the first day of exacerbation or when their condition permits. DISCUSSION: This trial will provide research methods to evaluate the clinical efficacy, safety, and the possible mechanism of YPF in the treatment of stable moderate-to-severe COPD patients. In addition, we hope to provide more possibilities for TCM to participate in the management of stable COPD. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry on 3 June 2022 (ChiCTR2200060476; date recorded: 3/6/2022, https://www.chictr.org.cn/ ).

Baloxavir marboxil use for critical human infection of avian influenza A H5N6 virus.

BACKGROUND: Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment. METHODS: Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed. FINDINGS: All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1 week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. CONCLUSIONS: For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness. FUNDING: This work was funded by the National Natural Science Foundation of China (81761128014).

Studying the Effect of Material and Geometry on Perceptual Outdoor Illumination.

Understanding and modeling perceived properties of sky-dome illumination is an important but challenging problem due to the interplay of several factors such as the materials and geometries of the objects present in the scene being observed. Existing models of sky-dome illumination focus on the physical properties of the sky. However, these parametric models often do not align well with the properties perceived by a human observer. In this work, drawing inspiration from the Hosek-Wilkie sky-dome model, we investigate the perceptual properties of outdoor illumination. For this purpose, we perform a large-scale user study via crowdsourcing to collect a dataset of perceived illumination properties (scattering, glare, and brightness) for different combinations of geometries and materials under a variety of outdoor illuminations, totaling 5,000 distinct images. We perform a thorough statistical analysis of the collected data which reveals several interesting effects. For instance, our analysis shows that when there are objects in the scene made of rough materials, the perceived scattering of the sky increases. Furthermore, we utilize our extensive collection of images and their corresponding perceptual attributes to train a predictor. This predictor, when provided with a single image as input, generates an estimation of perceived illumination properties that align with human perceptual judgments. Accurately estimating perceived illumination properties can greatly enhance the overall quality of integrating virtual objects into real scene photographs. Consequently, we showcase various applications of our predictor. For instance, we demonstrate its utility as a luminance editing tool for showcasing virtual objects in outdoor scenes.

EM-Gaze: eye context correlation and metric learning for gaze estimation.

In recent years, deep learning techniques have been used to estimate gaze-a significant task in computer vision and human-computer interaction. Previous studies have made significant achievements in predicting 2D or 3D gazes from monocular face images. This study presents a deep neural network for 2D gaze estimation on mobile devices. It achieves state-of-the-art 2D gaze point regression error, while significantly improving gaze classification error on quadrant divisions of the display. To this end, an efficient attention-based module that correlates and fuses the left and right eye contextual features is first proposed to improve gaze point regression performance. Subsequently, through a unified perspective for gaze estimation, metric learning for gaze classification on quadrant divisions is incorporated as additional supervision. Consequently, both gaze point regression and quadrant classification performances are improved. The experiments demonstrate that the proposed method outperforms existing gaze-estimation methods on the GazeCapture and MPIIFaceGaze datasets.

The complete chloroplast genome sequence of Viola kunawarensis Royle, a precious Uygur medicinal material.

Viola kunawarensis Royle is a precious Uygur medicinal material that has anti-fever and detoxifying effects. This study reports the complete chloroplast genome sequence of V. kunawarensis based on Illumina NovaSeq-PE150 platform sequencing reads. The genome is 156,837 bp long and contains a small single-copy (SSC) region of 17,059 bp and a large single-copy (LSC) region of 86,194 bp, separated by two inverted repeats (IRs) of 26,792 bp each. There are 111 unique genes in the chloroplast genome. In this study, V. kunawarensis was confirmed to be most closely related to all comprising Viola taxa except Viola mirabilis and Viola websteri.

Network Analysis Reveals the Combination of Controlled-Release and Regular Urea Enhances Microbial Interactions and Improves Maize Yields.

Increased complexity of microbial networks can contribute to increased biodiversity and multifunctionality and thus crop productivity. However, it is not clear which combination ratio of regular and controlled-release urea will increase the soil microbial community complexity and improve maize yield in the North China Plain. To address this knowledge gap, a 2-year field experiment was conducted to explore the effects of the combination of regular (U) and controlled release (S) urea ratios [no fertilizer control (CT), regular urea alone (U), controlled-release urea alone (S), controlled-release urea mixed with regular urea 3:7 (SU3), controlled-release urea mixed with regular urea 5:5 (SU5), and controlled-release urea mixed with regular urea 7:3 (SU7)] on XianYu 688 yield and its rhizosphere and bulk soil microbial community composition and network complexity at different fertility stages. The combination of controlled-release and regular urea increased the N agronomic efficiency, N partial factors productivity, maize yield, and grain number per spike, with the maximum maize yield (9,186 kg ha-1) being achieved when the ratio of controlled-release urea to regular urea was 3:7 (SU3, p < 0.05). Maize yield increased by 13% in the SU3 treatment compared to the CT treatment. Rhizosphere soil microbial diversity remained stable at the silking stage of maize while increased at the physiological maturity stage of maize, with the increasing controlled-release to regular N fertilizer ratios (from 3:7 to 7:3, p < 0.05). This result suggests that a combination of regular and controlled-release N fertilizer can still substantially increase soil microbial diversity in the later stages of maize growth. The combination of controlled-release and regular urea is more effective in improving microbial network total links and average degree, and N agronomic efficiency (R 2 = 0.79, p < 0.01), N partial factor productivity (R 2 = 0.79, p < 0.01), spikes per unit area (R 2 = 0.54, p < 0.05), and maize yield (R 2 = 0.42, p < 0.05) increased with the microbial network complexity. This result indicates that the higher microbial network complexity is strongly associated with the higher N agronomic efficiency and N partial factors productivity and maize yield. In conclusion, the ratio of controlled-release to regular urea at SU3 not only increases the yield of maize and N agronomic efficiency but also enhances microbial diversity and network complexity in the North China Plain.

Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19.

Background: The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19. Methods: We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels. Results: Eight pathogens, SARS-CoV-2, Aspergillus fumigatus (A. fumigatus), Mycoplasma orale (M. orale), Myroides odoratus (M. odoratus), Acinetobacter baumannii (A. baumannii), Candida tropicalis, herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens. Conclusions: For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.

CLPVG: Circular limited penetrable visibility graph as a new network model for time series.

A visibility graph transforms time series into graphs, facilitating signal processing by advanced graph data mining algorithms. In this paper, based on the classic limited penetrable visibility graph method, we propose a novel mapping method named circular limited penetrable visibility graph, which replaces the linear visibility line in limited penetrable visibility graph with nonlinear visibility arc for pursuing more flexible and reasonable mapping of time series. Tests on degree distribution and some common network features of the generated graphs from typical time series demonstrate that our circular limited penetrable visibility graph can effectively capture the important features of time series and show higher robust classification performance than the traditional limited penetrable visibility graph in the presence of noise. The experiments on real-world time-series datasets of radio and electroencephalogram signals also suggest that the structural features provided by a circular limited penetrable visibility graph, rather than a limited penetrable visibility graph, are more useful for time-series classification, leading to higher accuracy. This classification performance can be further enhanced through structural feature expansion by adopting subgraph networks. All of these results demonstrate the effectiveness of our circular limited penetrable visibility graph model.

Different Circulation Pattern of Multiple Respiratory Viruses in Southern China During the COVID-19 Pandemic.

China implemented stringent non-pharmaceutical interventions (NPIs) in spring 2020, which has effectively suppressed SARS-CoV-2. In this study, we utilized data from routine respiratory virus testing requests from physicians and examined circulation of 11 other respiratory viruses in Southern China, from January 1, 2018 to December 31, 2020. A total of 58,169 throat swabs from patients with acute respiratory tract infections (ARTIs) were collected and tested. We found that while the overall activity of respiratory viruses was lower during the period with stringent NPIs, virus activity rebounded shortly after the NPIs were relaxed and social activities resumed. Only influenza was effectively suppressed with very low circulation which extended to the end of 2020. Circulation of other respiratory viruses in the community was maintained even during the period of stringent interventions, especially for rhinovirus. Our study shows that NPIs against COVID-19 have different impacts on respiratory viruses.