Community centered public safety resilience under public emergencies: A case study of COVID-19.

During public emergencies, the level of public safety will be resilient and follow a process from decline to rise. Regarding the concept and influencing factors of public safety resilience, a three-level public safety resilience framework that includes personal, community, and government levels was proposed in this study. It provided the overall metrics that used the resistance and recovery ability to describe the dynamic characteristics of public safety resilience as well as the resilience assessment indexes on three levels. In the context of the Coronavirus Disease 2019 (COVID-19) pandemic, this study applied the proposed framework in a case study on public safety resilience at the Beihang community, Beijing, China through descriptive statistics, structural equation model, and principal component regression analysis of questionnaire data. The data analysis results showed that community resilience was the most important of the three levels of public safety resilience. In addition, community resilience could improve personal resilience, and government resilience had a positive effect on community and personal resilience. Compared with the resistance ability, the recovery ability was influenced more by the operation and improvement of the community. This study is conducive to understanding and improving public safety resilience on the personal, community, and government levels and can help relevant parties improve their ability to respond to the COVID-19 pandemic. Furthermore, the methods used in this study can be extended to other studies on public emergencies.

Gut-on-a-chip for disease models.

The intestinal tract is a vital organ responsible for digestion and absorption in the human body and plays an essential role in pathogen invasion. Compared with other traditional models, gut-on-a-chip has many unique advantages, and thereby, it can be considered as a novel model for studying intestinal functions and diseases. Based on the chip design, we can replicate the in vivo microenvironment of the intestine and study the effects of individual variables on the experiment. In recent years, it has been used to study several diseases. To better mimic the intestinal microenvironment, the structure and function of gut-on-a-chip are constantly optimised and improved. Owing to the complexity of the disease mechanism, gut-on-a-chip can be used in conjunction with other organ chips. In this review, we summarise the human intestinal structure and function as well as the development and improvement of gut-on-a-chip. Finally, we present and discuss gut-on-a-chip applications in inflammatory bowel disease (IBD), viral infections and phenylketonuria. Further improvement of the simulation and high throughput of gut-on-a-chip and realisation of personalised treatments are the problems that should be solved for gut-on-a-chip as a disease model.

Low acceptance rate of COVID-19 vaccination and reduced quality of life among heart transplant recipients during the COVID-19 pandemic.

OBJECTIVES: To investigate the impact of the current coronavirus disease 2019 (COVID-19) pandemic on the quality of life (QoL) and status of COVID-19 vaccination in heart transplant recipients (HTRs). METHODS: Patients who underwent allogeneic heart transplants between June 2006 and December 2019, who survived were selected from a follow-up registration form at our center. Data were collected using questionnaires in 2021, the QoL survey was conducted using the MOS 36-item Short-Form Health Survey (SF-36) and compared to the same time frame in 2019. The patients were divided into two groups: post-epidemic (A) and pre-epidemic (B) groups. We also recorded whether the participants had been vaccinated against COVID-19 (Beijing Sinovac COVID-19 vaccine). All the data obtained were analyzed. RESULTS: There were 88 patients who participated in the study. Only 12 (13.6%) were vaccinated. In terms of SF-36 scale assessments, after the outbreak of the COVID-19 pandemic, Group A scored lower in vitality [52.5(49.0, 58.0) vs. 75.0(69.0, 79.0), p < .001], social functioning [54.0(50.5, 58.0) vs. 74.0(67.5, 78.0), p < .001], role emotional [58.5(55.0, 62.0) vs. 67.0(63.0, 71.0), p < .001], and mental health [58.5(55.0, 62.0) vs. 76.0(72.0, 79.0), p < .001]. In Group A the mental component summary (MCS) significantly decreased [222.0(214.5, 230.0) vs. 289.0(277.5, 299.5), p < .001]. The PCS and MCS of HTRs who had been vaccinated against COVID-19 were significantly higher than those who had not [PCS: 283.5(280.0, 287.0) vs. 276.0(271.0, 279.0), p < .001; MCS: 245.0(141.5, 254.0) vs. 220.0(213.5, 226.5), p < .001]. CONCLUSION: Low acceptance levels of COVID-19 vaccination were observed in the HTRs. The QoL of the HTRs decreased after the COVID-19 pandemic.

Topoisomerase 2 inhibitor etoposide promotes interleukin-10 production in LPS-induced macrophages via upregulating transcription factor Maf and activating PI3K/Akt pathway.

Topoisomerase (TOP) inhibitors were commonly used as chemotherapeutic agents in the treatment of cancers. In our present study, we found that etoposide (ETO), a topoisomerase 2 (TOP2) inhibitor, upregulated the production of Interleukin 10 (IL-10) in lipopolysaccharide (LPS)-stimulated macrophages. Besides, other TOP2 inhibitors including doxorubicin hydrochloride (DOX) and teniposide (TEN) were also able to augment IL-10 production. Meanwhile, the expression levels of pro-inflammatory factors, for example IL-6 and TNF-α, were also decreased accordingly by the treatment of the TOP2 inhibitors. Of note, ETO facilitated IL-10 secretion, which might be regulated by transcription factor Maf via PI3K/AKT pathway, as pharmaceutic blockage of kinase PI3K or AKT attenuated ETO-induced Maf and IL-10 expression. Further, in LPS-induced mice sepsis model, the enhanced generation of IL-10 was observed in ETO-treated mice, whereas pro-inflammatory cytokines were decreased, which significantly reduced the mortality of mice from LPS-induced lethal cytokine storm. Taken together, these results indicated that ETO may exhibit an anti-inflammatory role by upregulating the alteration of transcription factor Maf and promoting subsequential IL-10 secretion via PI3K/Akt pathway in LPS-induced macrophages. Therefore, ETO may serve as a potential anti-inflammatory agent and employed to severe pro-inflammatory diseases including COVID-19.

Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.

Heightened innate immune responses in the respiratory tract of COVID-19 2 patients

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV44 2 infection has posed a severe threat to global public health. It is unclear how the human 45 immune system responds to this infection. Here, we used metatranscriptomic 46 sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight 47 COVID-19 cases. The expression of proinflammatory genes, especially chemokines, 48 was markedly elevated in COVID-19 cases compared to community-acquired 49 pneumonia patients and healthy controls,suggesting that SARS-CoV-2 infection causes 50 hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate 51 interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous 52 IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potential, with 53 overrepresentation of genes involved in inflammation. The transcriptome data was also 54 used to estimate immune cell populations, revealing increases in activated dendritic 55 cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection 3 56 could further our understanding of disease pathogenesis and point towards antiviral 57 strategies.