Needs, Challenges and Countermeasures of SARS-CoV-2 Surveillance in Cold-Chain Foods and Packaging to Prevent Possible COVID-19 Resurgence: A Perspective from Advanced Detections.

The pandemic caused by SARS-CoV-2 has a huge impact on the global economy. SARS-CoV-2 could possibly and potentially be transmitted to humans through cold-chain foods and packaging (namely good-to-human), although it mainly depends on a human-to-human route. It is imperative to develop countermeasures to cope with the spread of viruses and fulfil effective surveillance of cold-chain foods and packaging. This review outlined SARS-CoV-2-related cold-chain food incidents and current methods for detecting SARS-CoV-2. Then the needs, challenges and practicable countermeasures for SARS-CoV-2 detection, specifically for cold-chain foods and packaging, were underlined. In fact, currently established detection methods for SARS-CoV-2 are mostly used for humans; thus, these may not be ideally applied to cold-chain foods directly. Therefore, it creates a need to develop novel methods and low-cost, automatic, mini-sized devices specifically for cold-chain foods and packaging. The review intended to draw people's attention to the possible spread of SARS-CoV-2 with cold-chain foods and proposed perspectives for futuristic cold-chain foods monitoring during the pandemic.

Porcine Epidemic Diarrhea Virus Antagonizes Host IFN-λ-Mediated Responses by Tilting Transcription Factor STAT1 toward Acetylation over Phosphorylation To Block Its Activation.

Porcine epidemic diarrhea virus (PEDV) is the main etiologic agent causing acute swine epidemic diarrhea, leading to severe economic losses to the pig industry. PEDV has evolved to deploy complicated antagonistic strategies to escape from host antiviral innate immunity. Our previous study demonstrated that PEDV downregulates histone deacetylase 1 (HDAC1) expression by binding viral nucleocapsid (N) protein to the transcription factor Sp1, inducing enhanced protein acetylation. We hypothesized that PEDV inhibition of HDAC1 expression would enhance acetylation of the molecules critical in innate immune signaling. Signal transducer and activator of transcription 1 (STAT1) is a crucial transcription factor regulating expression of interferon (IFN)-stimulated genes (ISGs) and anti-PEDV immune responses, as shown by overexpression, chemical inhibition, and gene knockdown in IPEC-J2 cells. We further show that PEDV infection and its N protein overexpression, although they upregulated STAT1 transcription level, could significantly block poly(I·C) and IFN-λ3-induced STAT1 phosphorylation and nuclear localization. Western blotting revealed that PEDV and its N protein promote STAT1 acetylation via downregulation of HDAC1. Enhanced STAT1 acetylation due to HDAC1 inhibition by PEDV or MS-275 (an HDAC1 inhibitor) impaired STAT1 phosphorylation, indicating that STAT1 acetylation negatively regulated its activation. These results, together with our recent report on PEDV N-mediated inhibition of Sp1, clearly indicate that PEDV manipulates the Sp1-HDAC1-STAT1 signaling axis to inhibit transcription of OAS1 and ISG15 in favor of its replication. This novel immune evasion mechanism is realized by suppression of STAT1 activation through preferential modulation of STAT1 acetylation over phosphorylation as a result of HDAC1 expression inhibition. IMPORTANCE PEDV has developed sophisticated evasion mechanisms to escape host IFN signaling via its structural and nonstructural proteins. STAT1 is one of the key transcription factors in regulating expression of ISGs. We found that PEDV and its N protein inhibit STAT1 phosphorylation and nuclear localization via inducing STAT1 acetylation as a result of HDAC1 downregulation, which, in turn, dampens the host IFN signaling activation. Our study demonstrates a novel mechanism that PEDV evades host antiviral innate immunity through manipulating the reciprocal relationship of STAT1 acetylation and phosphorylation. This provides new insights into the pathogenetic mechanisms of PEDV and even other coronaviruses.

Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy.

Tumor-associated adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor-associated macrophages (TAMs) that support tumor development. Here, TAAs are engineered to promote the polarization of TAMs to the tumor suppressive M1 phenotype. Telratolimod, a toll-like receptor 7/8 agonist, is loaded into the lipid droplets of adipocytes to be released at the tumor site upon tumor cell-triggered lipolysis. Locally administered drug-loaded adipocytes increased tumor suppressive M1 macrophages in both primary and distant tumors and suppressed tumor growth in a melanoma model. Furthermore, drug-loaded adipocytes improved CD8+ T cell-mediated immune responses within the tumor microenvironment and favored dendritic cell maturation in the tumor draining lymph nodes.

How do knowledge diversity and ego-network structures affect firms' sustainable innovation: evidence from alliance innovation networks of China's new energy industries

Purpose>Facing the global public health emergency (GPHE), the conflict of cultural differences and the imbalance of vital resources such as knowledge among different organizations are becoming more severe, which affects the enthusiasm and sustainability of firms' innovation heavily. It is an urgent problem to be solved for firms how to make use of internal knowledge and external power to help firms' sustainable innovation (FSI). Thus, the purpose of this study is to deeply analyze how firms' internal knowledge diversity (KD) and external ego-network structures [ego-network density (ED) and honest brokers (HB)] affect FSI, as well as how the ego-network structures (ED and HB) moderate the relationship between KD and FSI based on the perspective of the ego network.Design/methodology/approach>Based on the data of the alliance innovation networks of China's new energy industries in 2009–2019, this study uses the social network analysis method and negative binomial regression model to explore the effect of KD and ego-network structures (ED and HB) on FSI, as well as the moderating effects of ego-network structures (ED and HB) on the relationship between KD and FSI based on the perspective of ego network.Findings>This study finds that KD, ED and HB can boost FSI. Moreover, ED plays a negative moderating role in the relationship between KD and FSI. However, the negative moderating effect of HB on the relationship between KD and FSI is not significant.Research limitations/implications>This study presents fresh empirical evidence and new insights for firms on how to make full use of firms' internal KD and external ego-network structures to facilitate FSI.Originality/value>First, this study not only enriches the research on the consequences of KD but also expands our understanding of the knowledge-based view to some extent. Second, this study not only enriches the motivation research of the FSI based on the perspective of ego-network in the context of the GPHE but also expands the application scope of social network theory and sustainable innovation' theory in part. Third, this paper is a new attempt to apply social network theory and knowledge-based view at the same time.

Impact of COVID-19 Risk Perception on Emotional Exhaustion among Chinese Hospitality Employees: The Mediating Effect of Job Insecurity.

This study aims to investigate the levels of COVID-19 risk perception (CVRP), job insecurity (JI), and emotional exhaustion (EE) among Chinese hospitality employees to examine the mediating effect of JI on the relationship between CVRP and EE. The moderating role of employee mindfulness (MF) and perceived employability (PE) have also be examined. Data were collected from 652 hospitality employees in Shandong and Jiangsu Province, China. We used structural equation modeling (SEM) to test the hypothesized relationship among the variables. Significant relationships were found between hospitality employees' CVRP and EE (ß = 0.103, p < 0.01), CVRP and JI (ß = 0.168, p < 0.001), and JI and EE (ß = 0.378, p < 0.001). According to the results, the higher level of the CVRP of hospitality employees, the higher level of the EE. In addition, results showed mediating effects of JI on the relationship between CVRP and EE. This study also found that MF buffered the positive relationship between CVRP and EE. Therefore, in the era of COVID-19, an effective support system at the organizational level is necessary to reduce JI and EE of hospitality employees.

Postoperative respiratory complications in SARS-CoV-2 positive pediatric patients across 20 United States hospitals: A Cohort Study.

INTRODUCTION: Data examining rates of postoperative complications among SARS-CoV-2 positive children are limited. The purpose of this study was to evaluate the impact of symptomatic and asymptomatic SARS-CoV-2 positive status on postoperative respiratory outcomes for children. METHODS: This retrospective cohort study included SARS-CoV-2 positive pediatric patients across 20 hospitals who underwent general anesthesia from March to October 2020. The primary outcome was frequency of postoperative respiratory complications, including: high-flow nasal cannula/non invasive ventilation, reintubation, pneumonia, Extracorporeal Membrane Oxygenation (ECMO), and 30-day respiratory-related readmissions or emergency department (ED) visits. Univariate analyses were used to evaluate associations between patient and procedure characteristics and stratified analyses by symptoms were performed examining incidence of complications. RESULTS: Of 266 SARS-CoV-2 positive patients, 163 (61.7%) were male, and the median age was 10 years (interquartile range 4-14). The majority of procedures were emergent or urgent (n = 214, 80.5%). The most common procedures were appendectomies (n = 78, 29.3%) and fracture repairs (n = 40,15.0%). 13 patients (4.9%) had preoperative symptoms including cough or dyspnea. 26 patients (9.8%) had postoperative respiratory complications, including 15 requiring high-flow oxygen, 8 with pneumonia, 4 requiring non invasive ventilation, 3 respiratory ED visits, and 2 respiratory readmissions. Respiratory complications were more common among symptomatic patients than asymptomatic patients (30.8% vs. 8.7%, p = 0.01). Higher ASA class and comorbidities were also associated with postoperative respiratory complications. CONCLUSIONS: Postoperative respiratory complications are less common in asymptomatic versus symptomatic SARS-COV-2 positive children. Relaxation of COVID-19-related restrictions for time-sensitive, non urgent procedures in selected asymptomatic patients may be reasonably considered. Additionally, further research is needed to evaluate the costs and benefits of routine testing for asymptomatic patients. LEVEL OF EVIDENCE: Iii, Respiratory complications.

Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice.

The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.

How Does Persuasion Happen? A Novel Bounded Confidence Opinion Dynamics Model Based on Social Judgment Theory

Persuasion exists in every aspect of social life. It is important to understand how persuasion works and how strong it is. In this article, we improve the classic Hegselmann-Krause model, one of the most famous bounded confidence models, and propose a novel opinion dynamics model to explain the process by which persuasion occurs from a systematic perspective. In our model, the concepts of latitudes of acceptance, noncommitment, and rejection from social judgment theory and the cognitive error in the process of persuasion, namely assimilation, are introduced. When people are exchanging their opinions with their neighbors, the opinions in the latitude of acceptance will be assimilated, those in the latitude of noncommitment will keep unchanged, and those in the latitude of rejection will not be considered. Theoretical proofs show that our model will converge to a stable state in a finite time. Numerical results of extensive simulation experiments on four datasets show the performance of the model. Furthermore, real social platform data and global COVID-19 vaccination data are analyzed to verify the effectiveness of the model in the decision-making process.

3’UTR of SARS-CoV-2 spike gene hijack host miR-296 or miR-520h to disturb cell proliferation and cytokine signaling

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has becoming globally public health threat. Recently studies were focus on SARS-CoV-2 RNA to design vaccine and drugs. It was demonstrated that virus RNA could play as sponge to host noncoding RNAs to regulate cellular processes. Bioinformatic research predicted a series of motif on SARS-CoV-2 genome where are targets of human miRNAs. In this study, we used dual-luciferase reporter assays to validate the interaction between 3’UTR of SARS-CoV-2 S (S-3’UTR) gene and bioinformatic predicted targeting miRNAs. The growth of 293T cells and HUVECs with overexpressed S-3’UTR was determined, while miRNAs and IL6, TNF-α levels were checked in this condition. Then, miR-296 and miR-602 mimic were introduced into 293T cells and HUVECs with overexpressed S-3’UTR, respectively, to reveal the underlying regulation mechanism. In results, we screened 19 miRNAs targeting the S-3’UTR, including miR-296 and miR-602. In 293T cell, S-3’UTR could inhibit 293T cell growth through down-regulation of miR-296. By reducing miR-602, S-3’UTR could induce HUVECs cell proliferation, alter the cell cycle, reduce apoptosis, and enhanced IL6 and TNF-αlevel. In conclusion, SARS-CoV-2 RNA could play as sponge of host miRNA to disturb cell growth and cytokine signaling. It suggests an important clue for designing COVID-19 drug and vaccine.

A Bioinformatic Approach Based on Systems Biology to Determine the Effects of SARS-CoV-2 Infection in Patients with Hypertrophic Cardiomyopathy

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide. While COVID-19 generally affects the lungs, it also damages other organs, including those of the cardiovascular system. Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disorder. Studies have shown that HCM patients with COVID-19 have a higher mortality rate;however, the reason for this phenomenon is not yet elucidated. Herein, we conducted transcriptomic analyses to identify shared biomarkers between HCM and COVID-19 to bridge this knowledge gap. Differentially expressed genes (DEGs) were obtained using the Gene Expression Omnibus ribonucleic acid (RNA) sequencing datasets, GSE147507 and GSE89714, to identify shared pathways and potential drug candidates. We discovered 30 DEGs that were common between these two datasets. Using a combination of statistical and biological tools, protein-protein interactions were constructed in response to these findings to support hub genes and modules. We discovered that HCM is linked to COVID-19 progression based on a functional analysis under ontology terms. Based on the DEGs identified from the datasets, a coregulatory network of transcription factors, genes, proteins, and microRNAs was also discovered. Lastly, our research suggests that the potential drugs we identified might be helpful for COVID-19 therapy.

Innovative Application of SERS in Food Quality and Safety: A Brief Review of Recent Trends.

Innovative application of surface-enhanced Raman scattering (SERS) for rapid and nondestructive analyses has been gaining increasing attention for food safety and quality. SERS is based on inelastic scattering enhancement from molecules located near nanostructured metallic surfaces and has many advantages, including ultrasensitive detection and simple protocols. Current SERS-based quality analysis contains composition and structural information that can be used to establish an electronic file of the food samples for subsequent reference and traceability. SERS is a promising technique for the detection of chemical, biological, and harmful metal contaminants, as well as for food poisoning, and allergen identification using label-free or label-based methods, based on metals and semiconductors as substrates. Recognition elements, including immunosensors, aptasensors, or molecularly imprinted polymers, can be linked to SERS tags to specifically identify targeted contaminants and perform authenticity analysis. Herein, we highlight recent studies on SERS-based quality and safety analysis for different foods categories spanning the whole food chain, 'from farm to table' and processing, genetically modified food, and novel foods. Moreover, SERS detection is a potential tool that ensures food safety in an easy, rapid, reliable, and nondestructive manner during the COVID-19 pandemic.

Cross-Sectional Associations between Living and Built Environments and Depression Symptoms among Chinese Older Adults

In this study, we explored the cross-sectional associations between living and built environments and depression among older Chinese adults. Data from 5822 participants were obtained. Depression symptoms were evaluated through the use of the Patient Health Questionnaire (PHQ-9), with a score higher than 4 categorized as having depression symptoms. The living environment was assessed by asking about dust in the environment and barrier-free facilities. We considered the presence of amenities within a 10 min walking distance and the proportion of green space within an 800 m distance from participants’ dwellings to reflect the built environment. Data were analyzed by multilevel logistic regression. Participants living in a non-dusty environment with proximity to green space had a lower risk of depression (non-dusty environment: OR = 0.784, 95% CI = 0.642, 0.956;green space: OR = 0.834, 95% CI = 0.697, 0.998). However, having no access to barrier-free facilities and hospital proximity increased the depression risk (barrier-free facilities: OR = 1.253, 95% CI = 1.078, 1.457;hospital: OR = 1.318, 95% CI = 1.104, 1.574). Dusty environments, access to barrier-free facilities and proximity to hospitals and green spaces were associated with depression symptoms among older Chinese adults.

CRISIS ventilator: A 3D printed option for ventilator surge in mass respiratory pandemics.

BACKGROUND: The COVID-19 pandemic revealed flaws in the stockpiling and distribution of ventilators. In this study, we assessed the durability, sterilizability, and performance of a 3D-printed ventilator. METHODS: SLS-printed devices were dropped from 1.83 m and autoclaved before evaluation on a COVID-19 simulated patient. The respiratory performance of an extrusion-printed device was studied using a variable compliance model. Ranges of sustainable respiratory rates were evaluated as a function of tidal volume. RESULTS: Autoclaving and dropping the device did not negatively impact minute ventilation or PIP for sustained ventilation. Equivalence was significant across all measures except for comparing the autoclaved and dropped with p = 0.06. Extrusion produced ventilators achieved minute ventilation ranging from 4.1 to 12.2 L/min for all simulated compliances; there was an inverse correlation between tidal volume and respiratory rate. CONCLUSION: The CRISIS ventilator is a durable, sterilizable, and reusable 3D-printed ventilator using off-the-shelf materials which could be employed variety of adult lung diseases. Further in-vivo testing is needed.

Measuring the impact of an exogenous factor: An exponential smoothing model of the response of shipping to COVID-19.

Following the outbreak of the COVID-19 pandemic, various lockdown strategies restrained global economic growth bringing a significant decline in maritime transportation. However, the previous studies have not adequately recognized the specific impacts of COVID-19 on maritime transportation. In this study, a series of analyses of the Baltic Dry Index (BDI), the China Coastal Bulk Freight Index (CCBFI) and of container throughputs with and without the impact of COVID-19 were carried out to assess changing trends in dry bulk and container transportation. The results show that global dry bulk transportation was largely affected by lockdown policies in the second month during COVID-19, and BDI presented a year-on-year decrease of approximately 35.5% from 2019 to 2020. The CCBFI showed an upward trend in the second month during COVID-19, one month ahead of the BDI. The container throughputs at Shanghai Port, the Ports of Hong Kong, the Ports of Singapore and the Ports of Los Angeles from 2019 to 2020 presented the largest year-on-year drops of approximately 19.6%, 7.1%, 10.6% and 30.9%, respectively. In addition, the authors developed exponential smoothing models of BDI, CCBFI, and container transportation, and calculated the percentage prediction error between the observed and predicted values to examine the impact of exogenous effects on the shipping industry due to the outbreak of COVID-19. The results are consistent with the conclusions obtained from the comparison of BDI, CCBFI, and container transportation during the same period in 2020 and 2019. Finally, on the basis of the findings, smart shipping and special support policies are proposed to reduce the negative impacts of COVID-19.

Analytical Performance Evaluation of Three Commercial Rapid Nucleic Acid Assays for SARS-CoV-2.

PURPOSE: To cope with the SARS-CoV-2 epidemic, several rapid nucleic acid assays have been approved for use, but the analytical performance has not been well evaluated. In this report, two key performance parameters, analytical sensitivity (limit of detection) and reproducibility, of three approved rapid nucleic acid assays were assessed using heat-inactivated SARS-CoV-2 culture supernatants quantified by digital PCR. METHODS: The LOD (limit of detection) and reproducibility of three approved rapid nucleic acid assays using their own instruments were assessed, while the LOD and reproducibility of two assays on a 7500 Real-Time instrument were assessed at the same time. RESULTS: Using their own instruments, 100% of samples with 1150 copies/mL viral RNA could be detected by the Da An and Coyote assays, while 90% of samples could be detected by the Ustar assay; yet, for 525 copies/mL and 287.5 copies/mL viral RNA, the detection rate of the Ustar assay was higher than that of either the Da An or Coyote assays. However, the three assays did not produce statistically significant results with the three different concentrations of viral RNA (P=0.46, 0.46 and 0.46). Using a 7500 Real-Time instrument, Da An and Coyote assays did not produce statistically significant results with the 1150, 525 and 287.5 copies/mL viral RNA (P>0.99, >0.99 and >0.99). The positive and negative detection rates of the three assays in the intra- and inter-assay stages were 100% on both their own instruments and the 7500 real-time PCR instrument. CONCLUSION: Positive or strongly positive samples can be detected by the rapid nucleic acid assay, but the analytical performance should be optimized, and comprehensive evaluations are also required.

Porcine Epidemic Diarrhea Virus Inhibits HDAC1 Expression To Facilitate Its Replication via Binding of Its Nucleocapsid Protein to Host Transcription Factor Sp1.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing acute intestinal infection in pigs, with high mortality often seen in neonatal pigs. The newborns rely on innate immune responses against invading pathogens because of lacking adaptive immunity. However, how PEDV disables the innate immunity of newborns toward severe infection remains unknown. We found that PEDV infection led to reduced expression of histone deacetylases (HDACs), especially HDAC1, in porcine IPEC-J2 cells. HDACs are considered important regulators of innate immunity. We hypothesized that PEDV interacts with certain host factors to regulate HDAC1 expression in favor of its replication. We show that HDAC1 acted as a negative regulator of PEDV replication in IPEC-J2 cells, as shown by chemical inhibition, gene knockout, and overexpression. A GC-box (GCCCCACCCCC) within the HDAC1 promoter region was identified for Sp1 binding in IPEC-J2 cells. Treatment of the cells with Sp1 inhibitor mithramycin A inhibited HDAC1 expression, indicating direct regulation of HDAC1 expression by Sp1. Of the viral proteins that were overexpressed in IPEC-J2 cells, the N protein was found to be present in the nuclei and more inhibitory to HDAC1 transcription. The putative nuclear localization sequence 261PKKNKSR267 contributed to its nuclear localization. The N protein interacted with Sp1 and interfered with its binding to the promoter region, thereby inhibiting its transcriptional activity for HDAC1 expression. Our findings reveal a novel mechanism of PEDV evasion of the host responses, offering implications for studying the infection processes of other coronaviruses. IMPORTANCE The enteric coronavirus porcine epidemic diarrhea virus (PEDV) causes fatal acute intestinal infection in neonatal pigs that rely on innate immune responses. Histone deacetylases (HDACs) play important roles in innate immune regulation. Our study found PEDV suppresses HDAC1 expression via the interaction of its N protein and porcine Sp1, which identified a novel mechanism of PEDV evasion of the host responses to benefit its replication. This study suggests that other coronaviruses, including SARS-CoV and SARS-CoV-2, also make use of their N proteins to intercept the host immune responses in favor of their infection.