COVID-19 Pandemic-Related Job Loss Impacts on Mental Health in South Korea.

OBJECTIVE: The economic hardship brought by the coronavirus disease-2019 (COVID-2019) pandemic has caused mental health problems among people of different socioeconomic status (SES). As social support helps to buffer these problems, we investigated the association between job loss related to COVID-19 and depression, anxiety, and suicidal thoughts; the differences in the effects according to SES; and the mediating effects of social support. METHODS: The effects of COVID-19-related job loss on depression, anxiety, and suicidal thoughts among 1,364 people were investigated through semi-structured and self-administered questionnaires: Patient Health Questionnaire-9, General Anxiety Disorder-7, and the Functional Social Support Questionnaire. Logistic regression and subgroup analyses were performed to assess the association between job loss and mental health status, and the moderating effects of income and educational levels. Moreover, the mediating effects of perceived social support on the association between job loss and depression, anxiety, and suicidal thoughts were analyzed. RESULTS: COVID-19-related job loss increased the risk of depression and suicidal thoughts. Adults with lower income and education level were at higher risk of depression, anxiety, and suicidal thoughts; perceived social support level had significant mediating effects on the association between job loss and depression/anxiety; and income level had significant moderating effects on this mediating pathway. CONCLUSION: COVID-19-related job loss were likely to be significantly associated with negative mental health outcomes, especially among individuals with low income and education levels. As social support had buffering effects on such outcomes, related government policies in cooperation with the governance of communities and stakeholders must be prepared.

Exploring Fear of Cancer Recurrence (FCR) in cancer survivors from a medical social work perspective: A qualitative study of medical social workers in South Korea.

BACKGROUND: Fear of Cancer Recurrence (FCR) in cancer survivors has been insufficiently addressed despite its imperativeness in cancer journey. Although several studies have investigated healthcare professionals' experience with FCR in cancer survivors, a medical social work perspective has rarely been reflected. This study aimed to explore Korean medical social workers' experience with intervening FCR in cancer survivors. METHODS: Snowball sampling recruited 12 experienced medical social workers intervening with cancer survivors at tertiary or university cancer hospitals in South Korea. Individual and focus-group interviews (FGI) were conducted with the medical social workers. The interviews were recorded, transcribed, and analyzed by using an inductive qualitative content analysis. RESULTS: Content analysis of the interviews extracted the following major themes regarding FCR in cancer survivors. First, when and how FCR among cancer survivors emerged at the early stage of medical social work interventions was identified. Second, how medical social workers dealt with FCR in cancer survivors was illustrated. Third, the responses of cancer survivors to medical social work interventions for FCR were assessed. Finally, the internal and external issues underlying the medical social work interventions for FCR among cancer survivors were revealed and discussed. CONCLUSION: Based on the results, this study suggested the implications on dealing with FCR in cancer survivors in the realm of medial social work profession. Furthermore, it expanded the discussion about FCR in cancer survivors from cancer hospitals to community.

Time-Series Trends of Depressive Levels of Korean Adults During the 2020 COVID-19 Pandemic in South Korea.

OBJECTIVE: This study aimed to observe the changes in people's depressive levels over 9 months since the coronavirus disease of 2019 (COVID-19) outbreak as well as to identify the predictors of people's depressive levels including COVID-19 infection fear in the context of South Korea in 2020. METHODS: For these purposes, four cross-sectional surveys were periodically implemented from March to December 2020. We randomly recruited 6,142 Korean adults (aged 19 to 70) by using a quota survey. Along with descriptive analysis, which included a one-way analysis of variance and correlations, multiple regression models were built to identify the predictors of people's depressive levels during the pandemic. RESULTS: Overall, people's depressive levels and fear of COVID-19 infection gradually increased since the COVID-19 outbreak. In addition to demographic variables (i.e., being a female, young age, unemployed, and living alone) and the duration of the pandemic, people's COVID-19 infection fear was associated with their depressive levels. CONCLUSION: To ameliorate these rising mental health issues, access to mental health services should be secured and expanded, particularly for individuals who present greater vulnerabilities due to socioeconomic characteristics that may affect their mental health.

Factors Related to Anxiety and Depression Among Adolescents During COVID-19: A Web-Based Cross-Sectional Survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak and subsequent disease-containment measures (such as school closures) significantly affected the lives of adolescents. We evaluated the mental-health status and factors associated with anxiety and depression among South Korean adolescents. METHODS: A nationwide online survey was conducted to evaluate the mental-health status of South Korean adolescents during the COVID-19 pandemic. In total, 570 adolescents aged 13-18 years were surveyed between May 27 and June 11, 2021. The participants completed the Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9) to determine anxiety and depression symptoms, respectively. Stepwise logistic regression models were constructed to determine factors related to anxiety and depression. RESULTS: Among the study participants, 11.2% and 14.2% had anxiety and depression, respectively. The results suggested that several factors, such as the experience of COVID-19 infection and quarantine of oneself, a family member or an acquaintance, physical and mental health problems, and fear of one's local community being discriminated against as a COVID-19 area were related to anxiety and depression. CONCLUSION: The present study identified COVID-19-related factors associated with anxiety and depression among adolescents, and provides insights regarding potential interventions to improve the mental health of adolescents. To promote the mental health of adolescents during the COVID-19 pandemic, special attention should be paid to individuals with physical or mental-health problems, and efforts should be made to reduce the negative social and emotional impacts of infection-control measures.

Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection.

The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved in the pathogenesis of IAV, but the specific mechanisms involved have not been clarified. Using confocal intravital microscopy in a mouse model of IAV infection, we observed profound neutrophil recruitment, platelet aggregation, neutrophil extracellular trap (NET) production and thrombin activation within the lung microvasculature in vivo. Importantly, deficiency or antagonism of the protease-activated receptor 4 (PAR4) reduced platelet aggregation, NET production, and neutrophil recruitment. Critically, inhibition of thrombin or PAR4 protected mice from virus-induced lung tissue damage and edema. Together, these data imply thrombin-stimulated platelets play a critical role in the activation/recruitment of neutrophils, NET release and directly contribute to IAV pathogenesis in the lung.

A Biodegradable Secondary Battery and its Biodegradation Mechanism for Eco-Friendly Energy-Storage Systems.

The production of rechargeable batteries is rapidly expanding, and there are going to be new challenges in the near future about how the potential environmental impact caused by the disposal of the large volume of the used batteries can be minimized. Herein, a novel strategy is proposed to address these concerns by applying biodegradable device technology. An eco-friendly and biodegradable sodium-ion secondary battery (SIB) is developed through extensive material screening followed by the synthesis of biodegradable electrodes and their seamless assembly with an unconventional biodegradable separator, electrolyte, and package. Each battery component decomposes in nature into non-toxic compounds or elements via hydrolysis and/or fungal degradation, with all of the biodegradation products naturally abundant and eco-friendly. Detailed biodegradation mechanisms and toxicity influence of each component on living organisms are determined. In addition, this new SIB delivers performance comparable to that of conventional non-degradable SIBs. The strategy and findings suggest a novel eco-friendly biodegradable paradigm for large-scale rechargeable battery systems.

Modulation of the liver immune microenvironment by the adeno-associated virus serotype 8 gene therapy vector.

Adeno-associated viruses (AAVs) are emerging as one of the vehicles of choice for gene therapy. However, the potential immunogenicity of these vectors is a major limitation of their use, leading to the necessity of a better understanding of how viral vectors engage the innate immune system. In this study, we demonstrate the immune response mediated by an AAV vector in a mouse model. Mice were infected intravenously with 4 × 1012 copies (cp)/kg of AAV8, and the ensuing immune response was analyzed using intravital microscopy during a period of weeks. Administration of AAV8 resulted in the infection of hepatocytes, and this infection led to a moderate, but significant, activation of the immune system in the liver. This host immune response involved platelet aggregation, neutrophil extracellular trap (NET) formation, and the recruitment of monocytes, B cells, and T cells. The resident liver macrophage population, Kupffer cells, was necessary to initiate this immune response, as its depletion abrogated platelet aggregation and NET formation and delayed the recruitment of immune cells. Moreover, the death of liver cells produced by this AAV was moderate and failed to result in a robust, sustained inflammatory response. Altogether, these data suggest that AAV8 is a suitable vector for gene therapy approaches.

Psychosocial Support during the COVID-19 Outbreak in Korea: Activities of Multidisciplinary Mental Health Professionals.

As of April 18, 2020, there have been a total of 10,653 confirmed cases and 232 deaths due to coronavirus disease 2019 (COVID-19) in Korea. The pathogen spread quickly, and the outbreak caused nationwide anxiety and shock. This study presented the anecdotal records that provided a detailed process of the multidisciplinary teamwork in mental health during the COVID-19 outbreak in the country. Psychosocial support is no less important than infection control during an epidemic, and collaboration and networking are at the core of disaster management. Thus, a multidisciplinary team of mental health professionals was immediately established and has collaborated effectively with its internal and external stakeholders for psychosocial support during the COVID-19 outbreak.

Large scale and integrated platform for digital mass culture of anchorage dependent cells.

Industrial applications of anchorage-dependent cells require large-scale cell culture with multifunctional monitoring of culture conditions and control of cell behaviour. Here, we introduce a large-scale, integrated, and smart cell-culture platform (LISCCP) that facilitates digital mass culture of anchorage-dependent cells. LISCCP is devised through large-scale integration of ultrathin sensors and stimulator arrays in multiple layers. LISCCP provides real-time, 3D, and multimodal monitoring and localized control of the cultured cells, which thereby allows minimizing operation labour and maximizing cell culture performance. Wireless integration of multiple LISCCPs across multiple incubators further amplifies the culture scale and enables digital monitoring and local control of numerous culture layers, making the large-scale culture more efficient. Thus, LISCCP can transform conventional labour-intensive and high-cost cell cultures into efficient digital mass cell cultures. This platform could be useful for industrial applications of cell cultures such as in vitro toxicity testing of drugs and cosmetics and clinical scale production of cells for cell therapy.

Visualizing Oncolytic Virus-Host Interactions in Live Mice Using Intravital Microscopy.

Oncolytic virus (OV) therapy is an emerging cancer treatment that uses replicating viruses to infect and kill tumor cells and incite anticancer immunity. While the approach shows promise, it currently fails most patients, indicating strategies to improve OV activity are needed. Developing these will require greater understanding of OV biology, particularly in the context of OV delivery and clearance, the infection process within a complex tumor microenvironment, and the modulation of anticancer immunity. To help achieve this, we have established a technique for high-resolution 4D imaging of OV-host interactions within intact tissues of live mice using intravital microscopy (IVM). We show that oncolytic vesicular stomatitis virus (VSV) directly labeled with Alexa Fluor dyes is easily visualized by single- or multiphoton microscopy while retaining bioactivity in vivo. The addition of fluorophore-tagged antibodies and genetically encoded reporter proteins to image target cells and the virus infection enables real-time imaging of dynamic interactions between VSV and host cells in blood, tumor, and visceral organs of live mice. The method has sufficient in vivo resolution to observe leukocytes in blood binding to and transporting VSV particles, foci of VSV infection spreading through a tumor, and antigen-presenting cells in the spleen interacting with and being infected by VSV. Visualizing OV-host interactions by IVM represents a powerful new tool for studying OV therapy.

Neutrophils in viral infection.

Neutrophils are the first wave of recruited immune cells to sites of injury or infection and are crucial players in controlling bacterial and fungal infections. Although the role of neutrophils during bacterial or fungal infections is well understood, their impact on antiviral immunity is much less studied. Furthermore, neutrophil function in tumor pathogenesis and cancer treatment has recently received much attention, particularly within the context of oncolytic virus infection where neutrophils produce antitumor cytokines and enhance oncolysis. In this review, multiple functions of neutrophils in viral infections and immunity are discussed. Understanding the role of neutrophils during viral infection may provide insight into the pathogenesis of virus infections and the outcome of virus-based therapies.

Platelets as Modulators of Inflammation.

Platelets have classically been considered crucial effector cells in hemostasis, but now are increasingly recognized as players during inflammatory responses in innate and adaptive immunity. Platelets can recognize and kill invading pathogens, and, upon stimulation, also release a wide array of mediators that modify immune and endothelial cell responses. Increased platelet activity can protect the host against infectious insults; however, the excessive activity can lead to inflammation-mediated tissue damage. These critical roles highlight the necessity of balancing the platelet response at the intersection of hemostasis and inflammation. In this review, the authors present the current understanding of the inflammatory role of platelets. They also highlight recent findings on a modulator that links inflammation and deleterious tissue damage in disease pathogenesis.

Necrostatin-1 Protects Against D-Galactosamine and Lipopolysaccharide-Induced Hepatic Injury by Preventing TLR4 and RAGE Signaling.

Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome results in massive inflammation and hepatocyte death. Necroptosis is a regulated form of necrotic cell death that is emerging as a crucial control point for inflammatory diseases. The kinases receptor interacting protein (RIP) 1 and RIP3 are known as key modulators of necroptosis. In this study, we investigated the impact of necroptosis in the pathogenesis of FHF and molecular mechanisms, particularly its linkage to damage-associated molecular pattern (DAMP)-mediated pattern recognition receptor (PRR) signaling pathways. Male C57BL/6 mice were given an intraperitoneal injection of necrostatin-1 (Nec-1, RIP1 inhibitor; 1.8 mg/kg; dissolved in 2% dimethyl sulfoxide in phosphate-buffered saline) 1 h before receiving D-galactosamine (GalN; 800 mg/kg)/lipopolysaccharide (LPS; 40 µg/kg). Hepatic RIP1, RIP3 protein expression, their phosphorylation, and RIP1/RIP3 complex formation upregulated in the GalN/LPS group were attenuated by Nec-1. Nec-1 markedly reduced the increases in mortality and serum alanine aminotransferase activity induced by GalN/LPS. Increased serum high mobility group box 1 (HMGB1) and interleukin (IL)-33 release, HMGB1-toll-like receptor 4 and HMGB1-receptor for advanced glycation end products (RAGE) interaction, and nuclear protein expressions of NF-κB and early growth response protein-1 (egr-1) were attenuated by Nec-1. Our finding suggests that necroptosis is responsible for GalN/LPS-induced liver injury through DAMP-activated PRR signaling.

Genipin protects d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the necroptosis-mediated inflammasome signaling.

Acute liver failure (ALF) is a life-threatening syndrome resulting from massive inflammation and hepatocyte death. Necroptosis, a programmed cell death controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, has been shown to play an important role in regulating inflammation via crosstalk between other intracellular signaling. The inflammasome is a major intracellular multiprotein that induces inflammatory responses by mediating immune cell infiltration, thus potentiating injury. Genipin, a major active compound of the gardenia fruit, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties. This study investigated the hepatoprotective mechanisms of genipin on d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced ALF, particularly focusing on interaction between necroptosis and inflammasome. Mice were given an intraperitoneal injection of genipin (25, 50, and 100mg/kg) or necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.8mg/kg) 1h prior to GalN (800mg/kg)/LPS (40µg/kg) injection and were killed 3h after GalN/LPS injection. Genipin improved the survival rate and attenuated increases in serum aminotransferase activities and inflammatory cytokines after GalN/LPS injection. Genipin reduced GalN/LPS-induced increases in RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome complex, similar to the effects of Nec-1. GalN/LPS significantly increased serum levels of high-mobility group box 1 and interleukin (IL)-33, which were attenuated by genipin and Nec-1. Moreover, similar to Nec-1, genipin attenuated GalN/LPS-induced increases in the protein expression levels of NLRP3, ASC, and caspase-1, inflammasome components, and levels of liver and serum IL-1ß. Taken together, our findings suggest that genipin ameliorates GalN/LPS-induced hepatocellular damage by suppressing necroptosis-mediated inflammasome signaling.

Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice.

Neutrophil extracellular traps (NETs; webs of DNA coated in antimicrobial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multicolor confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo. NETs were critical for the development of sepsis-induced intravascular coagulation regardless of the inciting bacterial stimulus (gram-negative, gram-positive, or bacterial products). Removal of NETs via DNase infusion, or in peptidylarginine deiminase-4-deficient mice (which have impaired NET production), resulted in significantly lower quantities of intravascular thrombin activity, reduced platelet aggregation, and improved microvascular perfusion. NET-induced intravascular coagulation was dependent on a collaborative interaction between histone H4 in NETs, platelets, and the release of inorganic polyphosphate. Real-time perfusion imaging revealed markedly improved microvascular perfusion in response to the blockade of NET-induced coagulation, which correlated with reduced markers of systemic intravascular coagulation and end-organ damage in septic mice. Together, these data demonstrate, for the first time in an in vivo model of infection, a dynamic NET-platelet-thrombin axis that promotes intravascular coagulation and microvascular dysfunction in sepsis.

Role of platelets in neutrophil extracellular trap (NET) production and tissue injury.

In addition to their well-known role as the cellular mediator of thrombosis, numerous studies have identified key roles for platelets during various disease processes. Importantly, platelets play a critical role in the host immune response, directly interacting with, and eliminating pathogens, from the blood stream. In addition to pathogen clearance, platelets also contribute to leukocyte recruitment at sites of infection and inflammation, and modulate leukocyte activity. Platelet interaction with activated neutrophils is a potent inducer of neutrophil extracellular trap (NET). NETs consist of a diffuse, sticky web of extracellular DNA, nuclear and granular proteins, and serve to ensnare and kill pathogens. In addition to catching pathogens, the cytotoxic molecules and proteases on NETs have the potential to inflict significant tissue damage. Additionally, NET components have been suggested to be key activators of infection-induced coagulopathy. These critical roles, at the interface between hemostasis and immunity, highlight the need for balance in the platelet response; too little platelet activity results in bleeding and immune deficit, too much leads to tissue pathogenesis. In this review, we highlight recent advances in our understanding of the role platelets play in inflammation, the link between platelets and NETs and the role platelets play in disease pathogenesis.

Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion.

Ischemia and reperfusion (I/R) is a complex phenomenon involving massive inflammation and cell death. Necroptosis refers to a newly described cell death as "programmed necrosis" that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases. Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli and involves crosstalk between different modes of cell death and inflammation. In this study, we investigated pattern changes in necroptosis and its role in autophagy signaling during hepatic I/R. Male C57BL/6 mice were subjected to 60min of ischemia followed by 3h reperfusion. Necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.65mg/kg) was administered intraperitoneally 5min before reperfusion. Hepatic I/R significantly increased the level of RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome formation, which were attenuated by Nec-1. I/R also significantly increased serum levels of alanine aminotransferase, tumor necrosis factor-α, and interleukin-6, which were attenuated by Nec-1. Meanwhile, hepatic I/R activated autophagy and mitophagy, as evidenced by increased LC3-II, PINK1, and Parkin, and decreased sequestosome 1/p62 protein expression. Nec-1 attenuated these changes and attenuated the increased levels of autophagy-related protein (ATG) 3, ATG7, Rab7, and cathepsin B protein expression during hepatic I/R. Moreover, hepatic I/R activated the extracellular signal-regulated kinase (ERK) pathway, and Nec-1 attenuated this increase. Taken together, our findings suggest that necroptosis contributes to hepatic damage during I/R, which induces autophagy via ERK activation.

Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh.

Heart failure remains a major public health concern with a 5-year mortality rate higher than that of most cancers. Myocardial disease in heart failure is frequently accompanied by impairment of the specialized electrical conduction system and myocardium. We introduce an epicardial mesh made of electrically conductive and mechanically elastic material, to resemble the innate cardiac tissue and confer cardiac conduction system function, to enable electromechanical cardioplasty. Our epicardium-like substrate mechanically integrated with the heart and acted as a structural element of cardiac chambers. The epicardial device was designed with elastic properties nearly identical to the epicardial tissue itself and was able to detect electrical signals reliably on the moving rat heart without impeding diastolic function 8 weeks after induced myocardial infarction. Synchronized electrical stimulation over the ventricles by the epicardial mesh with the high conductivity of 11,210 S/cm shortened total ventricular activation time, reduced inherent wall stress, and improved several measures of systolic function including increases of 51% in fractional shortening, ~90% in radial strain, and 42% in contractility. The epicardial mesh was also capable of delivering an electrical shock to terminate a ventricular tachyarrhythmia in rodents. Electromechanical cardioplasty using an epicardial mesh is a new pathway toward reconstruction of the cardiac tissue and its specialized functions.

Wearable red-green-blue quantum dot light-emitting diode array using high-resolution intaglio transfer printing.

Deformable full-colour light-emitting diodes with ultrafine pixels are essential for wearable electronics, which requires the conformal integration on curvilinear surface as well as retina-like high-definition displays. However, there are remaining challenges in terms of polychromatic configuration, electroluminescence efficiency and/or multidirectional deformability. Here we present ultra-thin, wearable colloidal quantum dot light-emitting diode arrays utilizing the intaglio transfer printing technique, which allows the alignment of red-green-blue pixels with high resolutions up to 2,460 pixels per inch. This technique is readily scalable and adaptable for low-voltage-driven pixelated white quantum dot light-emitting diodes and electronic tattoos, showing the best electroluminescence performance (14,000 cd m(-2) at 7 V) among the wearable light-emitting diodes reported up to date. The device performance is stable on flat, curved and convoluted surfaces under mechanical deformations such as bending, crumpling and wrinkling. These deformable device arrays highlight new possibilities for integrating high-definition full-colour displays in wearable electronics.