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1.
Energies ; 16(3):1074, 2023.
Article in English | MDPI | ID: covidwho-2199931

ABSTRACT

Elevated medical waste has urged the improvement of sustainable medical waste treatments. A bibliometric analysis is initially conducted to investigate scientific development of medical waste management to pinpoint the publication trends, influential articles, journals and countries and study hotspots. Publications on medical waste and its management sharply increased since 2020. The most influential article was written by Klemešet al., and 'Waste Management and Research';is the most productive journal. India, China, the United Kingdom, Iran and Italy have published the most works. The research spotlights have switched from 'human';and 'sustainable development';in 2019 to 'COVID-19';and 'circular economy';in 2021. Since government acts essentially in handling medical waste and controlling disease transmission, rule implementations among the abovementioned countries are summarized to seek gaps between scientific advancement and regulatory frameworks. For accomplishing a circular economy, waste-to-energy technologies (incineration, gasification, pyrolysis, plasma-based treatments, carbonization, hydrogenation, liquefaction, biomethanation, fermentation and esterification) are comprehensively reviewed. Incineration, gasification, pyrolysis and carbonization are relatively feasible methods, their characteristics and limitations are further compared. By holistically reviewing current status of medical waste research, the focal points involved in management at the policy and technical level have been highlighted to find proper routes for medical waste valorization.

2.
Smart Materials in Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-2120031

ABSTRACT

Nowadays, malignant brain tumors are still mostly lethal diseases with poor prognosis and a clinical median survival rate of fewer than 2 years after therapeutic intervention. It is difficult to achieve complete remission of brain tumors due to blood-brain barrier (BBB) and a lack of efficient drug delivery systems to targeted transportation of brain tumor medicines. Nanoparticle delivery systems have shown merits including stability and high carrier capacity for the transportation of different drugs to treat brain tumors. The application of mRNA nanomedicines brings in great promise not only in COVID-19, but also for malignant brain tumor immunotherapy. The appropriate delivery system facilitates mRNA delivery efficiency and enhances the immune response successfully, for optimal treatment outcomes on malignant brain tumors. Herein, we do an updated review on the development of mRNA nanomedicines for malignant brain cancer treatment. We focus on how to design mRNA-loaded nanoparticle-based delivery systems with optimized pharmacokinetics and pharmacodynamics for efficient therapy of brain cancers. In addition, we point out the challenges and solutions for further development of mRNA nanomedicines for brain cancer therapy. We hope this review would stimulate interest among researchers with different backgrounds and expedite the translation from bench to bedside for the mRNA nanomedicines.

3.
Health data science ; 2022, 2022.
Article in English | EuropePMC | ID: covidwho-2112030

ABSTRACT

Background During the COVID-19 pandemic, mental health concerns (such as fear and loneliness) have been actively discussed on social media. We aim to examine mental health discussions on Twitter during the COVID-19 pandemic in the US and infer the demographic composition of Twitter users who had mental health concerns. Methods COVID-19-related tweets from March 5th, 2020, to January 31st, 2021, were collected through Twitter streaming API using keywords (i.e., “corona,” “covid19,” and “covid”). By further filtering using keywords (i.e., “depress,” “failure,” and “hopeless”), we extracted mental health-related tweets from the US. Topic modeling using the Latent Dirichlet Allocation model was conducted to monitor users' discussions surrounding mental health concerns. Deep learning algorithms were performed to infer the demographic composition of Twitter users who had mental health concerns during the pandemic. Results We observed a positive correlation between mental health concerns on Twitter and the COVID-19 pandemic in the US. Topic modeling showed that “stay-at-home,” “death poll,” and “politics and policy” were the most popular topics in COVID-19 mental health tweets. Among Twitter users who had mental health concerns during the pandemic, Males, White, and 30-49 age group people were more likely to express mental health concerns. In addition, Twitter users from the east and west coast had more mental health concerns. Conclusions The COVID-19 pandemic has a significant impact on mental health concerns on Twitter in the US. Certain groups of people (such as Males and White) were more likely to have mental health concerns during the COVID-19 pandemic.

4.
Front Med (Lausanne) ; 9: 874611, 2022.
Article in English | MEDLINE | ID: covidwho-2115469

ABSTRACT

The global epidemic has been controlled to some extent, while sporadic outbreaks still occur in some places. It is essential to summarize the successful experience and promote the development of new drugs. This study aimed to explore the common mechanism of action of the four Chinese patent medicine (CPMs) recommended in the Medical Observation Period COVID-19 Diagnostic and Treatment Protocol and to accelerate the new drug development process. Firstly, the active ingredients and targets of the four CPMs were obtained by the Chinese medicine composition database (TCMSP, TCMID) and related literature, and the common action targets of the four TCMs were sorted out. Secondly, the targets of COVID-19 were obtained through the gene-disease database (GeneCards, NCBI). Then the Venn diagram was used to intersect the common drug targets with the disease targets. And GO and KEGG pathway functional enrichment analysis was performed on the intersected targets with the help of the R package. Finally, the results were further validated by molecular docking and molecular dynamics analysis. As a result, a total of 101 common active ingredients and 21 key active ingredients of four CPMs were obtained, including quercetin, luteolin, acacetin, kaempferol, baicalein, naringenin, artemisinin, aloe-emodin, which might be medicinal substances for the treatment of COVID-19. TNF, IL6, IL1B, CXCL8, CCL2, IL2, IL4, ICAM1, IFNG, and IL10 has been predicted as key targets. 397 GO biological functions and 166 KEGG signaling pathways were obtained. The former was mainly enriched in regulating apoptosis, inflammatory response, and T cell activation. The latter, with 92 entries related to COVID-19, was mainly enriched to signaling pathways such as Coronavirus disease-COVID-19, Cytokine-cytokine receptor interaction, IL-17 signaling pathway, and Toll-like receptor signaling pathway. Molecular docking results showed that 19/21 of key active ingredients exhibited strong binding activity to recognized COVID-19-related targets (3CL of SARS-CoV-2, ACE2, and S protein), even better than one of these four antiviral drugs. Among them, shinflavanone had better affinity to 3CL, ACE2, and S protein of SARS-CoV-2 than these four antiviral drugs. In summary, the four CPMs may play a role in the treatment of COVID-19 by binding flavonoids such as quercetin, luteolin, and acacetin to target proteins such as ACE2, 3CLpro, and S protein and acting on TNF, IL6, IL1B, CXCL8, and other targets to participate in broad-spectrum antiviral, immunomodulatory and inflammatory responses.

5.
Medicine (Baltimore) ; 101(39): e30844, 2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2113747

ABSTRACT

BACKGROUND: From the end of 2019 to now, coronavirus disease 2019 (COVID-19) has put enormous strain on the world's health systems. As a characteristic sign of COVID-19 patient, olfactory dysfunction (OD) poses considerable problems for patients. In China, acupuncture has been widely used to treat OD caused by COVID-19, but there is still a lack of evidence-based medical evaluation. This study was designed to evaluate the effectiveness and safety of acupuncture for the treatment of COVID-19 OD. METHODS: According to the retrieval strategies, randomized controlled trials on the acupuncture for COVID-19 OD were obtained from Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database and the Wanfang Database, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using Review Manager (RevMan 5.3) and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide up-to-date summary proof for evaluating the effectiveness and safety of acupuncture for COVID-19 OD.


Subject(s)
Acupuncture Therapy , COVID-19 , Olfaction Disorders , Acupuncture Therapy/methods , COVID-19/complications , COVID-19/therapy , Disease Progression , Humans , Meta-Analysis as Topic , Research Design , Systematic Reviews as Topic , Treatment Outcome
6.
Phys Rev E ; 106(4-1): 044409, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2107721

ABSTRACT

We use direct coupling analysis (DCA) to determine epistatic interactions between loci of variability of the SARS-CoV-2 virus, segmenting genomes by month of sampling. We use full-length, high-quality genomes from the GISAID repository up to October 2021 for a total of over 3 500 000 genomes. We find that DCA terms are more stable over time than correlations but nevertheless change over time as mutations disappear from the global population or reach fixation. Correlations are enriched for phylogenetic effects, and in particularly statistical dependencies at short genomic distances, while DCA brings out links at longer genomic distance. We discuss the validity of a DCA analysis under these conditions in terms of a transient auasilinkage equilibrium state. We identify putative epistatic interaction mutations involving loci in spike.

7.
Front Public Health ; 10: 1015316, 2022.
Article in English | MEDLINE | ID: covidwho-2099276

ABSTRACT

Background: In March 2022, Shanghai, China, was hit by a severe wave of SARS-CoV-2 transmission caused by the Omicron variant strain. The medical staff was greatly infected during this period, which posed a traumatic event for them. Meanwhile, they also experience post-traumatic growth under introspection and positive change. However, the psychological coping and growth after infection with COVID-19 among medical staff have rarely been investigated. Objectives: To explore the process and influencing factors of post-traumatic growth among emergency nurses infected with coronavirus disease (COVID-19) so as to provide a new perspective and theoretical basis for psychological rehabilitation or intervention for medical staff who experienced traumatic events. Methods: The study used a qualitative design based on the phenomenological approach. A purposive sampling method was used to explore the subjective feelings and post-traumatic growth among 13 first-line emergency nurses infected with COVID-19 in Shanghai, China. Semi-structured face-to-face interviews were conducted in June 2022. A Seven-step Colaizzi process was used for data analysis. Results: Themes were described and extracted from the experience and insights at different stages during the fight against the virus. Three main themes, i.e., stress period, adjustment period, and growth period, as well as several sub-themes, were identified. Conclusion: First-line emergency nurses infected with COVID-19 are a sensitive group that should be given more attention. Investigating how they achieve psychological adjustment and growth in the case of severe trauma can provide valuable references for nursing management and education in the future. Society, hospital and nursing managers should pay more attention to the PTG of nurses and establish supportive PTG strategies, which will benefit the retention rate and career development of nurses.


Subject(s)
COVID-19 , Nursing Staff, Hospital , Posttraumatic Growth, Psychological , Humans , SARS-CoV-2 , COVID-19/epidemiology , Nursing Staff, Hospital/psychology , China/epidemiology
8.
Journal of Brand Management ; 2022.
Article in English | Web of Science | ID: covidwho-2096910

ABSTRACT

This paper examines the relations among AI service attributes, brand image, brand familiarity and customer equity. The proposed relationships were tested by structural equation modeling of survey data of 210 usable responses in China. Test results indicate that problem-solving ability, accuracy, and customization of AI service have significant positive effects on brand image;the three constructs of customer equity (value equity, brand equity, and relationship equity) are all positively and strongly affected by brand image. Moreover, brand familiarity moderates the effect of customization, interaction, and problem-solving ability on brand image. By bringing together AI literature and consumer behavior literature, this research sheds light on the effectiveness of AI service in enhancing brand image and customer equity. This has important theoretical value in enriching the streams of AI and brand research. Additionally, this research integrates the AI technology within a corporate brand management strategy and offers practitioners and marketers in post-COVID era with a model with which they can find new ways to meet consumer demands and improve brand image via AI technology.

9.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-2045785

ABSTRACT

Background In early 2022, an outbreak of Coronavirus Disease 2019 (COVID-19) occurred in Shanghai, China. The spread of the epidemic put a large amount of stress on the local healthcare system, especially emergency nurses (ENs), which may affect their well-being and performance. Enhancing the psychological resilience of ENs during COVID-19 pandemic may improve job satisfaction, retention, and public health emergency response. However, few studies have researched the perception and psychological resilience of ENs during COVID-19 pandemic. Objective To understand ENs' perception and psychological resilience and their coping strategies with adversity during COVID-19 in Shanghai, as well as factors associated with psychological resilience. Methods This qualitative study was conducted using a phenomenological approach. A total of 17 ENs from a 3rd level hospital in Shanghai were selected using a method of purposive sampling. Between April and May 2022, in-depth semi-structured interviews and Colaizzi seven-step method were performed for data collection and analysis. Results The investigation discovered three themes and nine subthemes. The first theme is “risk factors.” Risk factors for ENs to remain resilience are sudden multiplication of workload, stressful of screening of infected patients, and the support nurses being unfamiliar with the procedure. The second theme is “promoting factors.” ENs emphasized the importance of management assurance and humanistic care, as well as social support. They recognized adversity and resilience, and used self-management strategies to cope with the situation. The third theme is “motivated by altruism.” ENs were driven by altruism to respond to adversity with a positive attitude. They realized their self-worth by helping patients with a sense of sacred mission. Conclusions Psychological resilience is not a stable psychological characteristic but a constantly changing process that is affected by internal and external factors. Enhancing resilience of ENs during the COVID-19 pandemic may improve work satisfaction, retention, and public health emergency response. Adequate preparation before a pandemic, reasonable arrangement, a trustworthy working atmosphere, encouragement and improvement of individual and collective strategies for nurses to cope with adversity, timely rewards, and nurse empowerment, as well as counseling and training, can be used to enhance psychological resilience of ENs.

10.
Clin Interv Aging ; 17: 1365-1378, 2022.
Article in English | MEDLINE | ID: covidwho-2043232

ABSTRACT

COVID-19 pandemic significantly threatens the health and well-being of older adults. Aging-related changes, including multimorbidity, weakened immunity and frailty, may make older people more susceptible to severe infection and place them at higher risk of morbidity and mortality from COVID-19. Various quarantine measures have been implemented to control the spread of COVID-19. Nevertheless, such social distancing has disrupted routine health care practices, such as accessibility of medical services and long-term continuous care services. The medical management of older adults with multimorbidity is significantly afflicted by COVID-19. Older persons with frailty or multiple chronic disease may poorly adapt to the altered health care system, having detrimental consequences on their physical and mental health. COVID-19 pandemic has posed great challenges to the health of older adults. We highlighted the difficulties and obstacles of older adults during this unprecedented time. Also, we provided potential strategies and recommendations for actions to mitigate the COVID-19 pandemic threats. Certain strategies like community primary health care, medication delivery and home care support are adopted by many health facilities and caregivers, whereas other services such as internet hospital and virtual medical care are promoted to be accessible in many regions. However, guidelines and policies based on high-quality data are still needed for better health promotion of older groups with increasing resilience during the COVID-19 pandemic.


Subject(s)
COVID-19 , Frailty , Aged , Aged, 80 and over , Delivery of Health Care , Health Facilities , Humans , Pandemics/prevention & control , SARS-CoV-2
11.
Chemosphere ; 308(Pt 3): 136461, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2031191

ABSTRACT

Because of the current COVID-19 outbreak all over the world, the problem of antiviral drugs entering water has become increasingly serious. Arbidol hydrochloride (ABLH) is one of the most widely used drugs against COVID-19, which has been detected in sewage treatment plant sediments after the COVID-19 outbreak. However, there has been no report on the degradation of ABLH. In order to remove ABLH we prepared a novel photocatalyst composed of Ti3C2 MXene and supramolecular g-C3N4 (TiC/SCN) via a simple method. The properties of the material were studied by a series of characterizations (SEM, TEM, EDS, XRD, FTIR, UV-vis, DRS, XPS, TPC, PL, EIS and UPS), indicating the successful preparation of TiC/SCN. Results show that 99% of ABLH was removed within 150 min under visible light illumination by the 0.5TiC/SCN (containing 0.5% of TiC). The performance of 0.5TiC/SCN was about 2.66 times that of SCN resulting from the formation of Schottky junction. Furthermore, under real sunlight illumination, 99.2% of ABLH could be removed by 0.5TiC/SCN within 120 min, which was better than that of commercial P25 TiO2. The pH, anions (NO3- and SO42-) and dissolved organic matter (fulvic acid) could significantly affect the ABLH degradation. Moreover, three possible degradation pathways of ABLH were proposed, and the toxicities of the corresponding by-products were less toxic than ABLH. Meanwhile, findings showed that the superoxide radicals played a major role in the photocatalytic degradation of ABLH by 0.5TiC/SCN. This study provides a well understanding of the mechanism of ABLH degradation and provides a valuable reference for the treatment of ABLH in water.


Subject(s)
COVID-19 , Titanium , Antiviral Agents , Catalysis , Humans , Indoles , Light , Sewage , Sulfides , Superoxides , Titanium/chemistry , Water
12.
Signal Transduct Target Ther ; 7(1): 318, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2028663

ABSTRACT

Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were found to bind MASP-2, a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein. Complement hyperactivation was also observed in SARS-CoV-2-infected patients. Either blocking the N protein:MASP-2 interaction, MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo. Altogether, these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.


Subject(s)
COVID-19 , Lung Injury , Animals , COVID-19/genetics , Complement Pathway, Mannose-Binding Lectin/genetics , Coronavirus Nucleocapsid Proteins , Humans , Inflammation/genetics , Mannose-Binding Protein-Associated Serine Proteases/genetics , Mannose-Binding Protein-Associated Serine Proteases/metabolism , Mice , SARS-CoV-2
13.
International Journal of Music Education ; 2022.
Article in English | Web of Science | ID: covidwho-2020817

ABSTRACT

The purpose of this study was to examine graduate instrumentalists' practice habits, motivation orientations, and the impact of COVID-19 pandemic on their instrumental practice. Data were collected for this qualitative descriptive study through four participants' videotaped practice recordings (N = 4), video-stimulated recall (n = 4), semi-structured interviews (n = 4), and a questionnaire (n = 4) about practice strategies adopted and motivation orientations. Four themes were emergent including (a) task-oriented practice routines, (b) solution-oriented approaches, (c) mixed motivations, and (d) challenges faced during COVID-19 pandemic. Results indicated that the COVID-19 pandemic negatively impacted graduate instrumentalists' practice progress and psychological state. Their experience could be a reference for other instrumentalists in applying effective practice strategies and achieving strong and independent musicianship. The findings of this study also suggested that instrumental instructors may consider encouraging their students to flexibly plan practice routines and give priority to short-term goals.

14.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1980780

ABSTRACT

Background As the COVID-19 pandemic continues, online learning and long-term isolation from social and clinical settings has exacerbated mental health problems and symptoms of academic burnout among medical students. However, few studies have discussed symptoms of academic burnout as a result of reduced social support, and increased stress among medical students during the process of online learning. To fill this gap, this study investigated the influencing factors and mechanism of academic burnout in medical students' online learning process. Both the positive inhibition effect of positive factors such as social support, and the negative aggravation effect of negative factors such as stress were explored, while the mediating and protecting role of resilience is also discussed. Method We collected survey data from a total of 817 medical students from a medical school in China who participated in online learning during the fall 2021 semester. An online questionnaire was sent to the students in January, 2022. Items adapted from the DASS Scale developed by Lovibond and Lovibond were used to measure medical students' stress levels. The perceived social support of medical students was assessed by the Gregory MSPSS. Resilience was evaluated by the 10-Item Connor–Davidson Resilience Scale (CD-RISC). Items from the Maslach Burnout Inventory–Student Survey (MBI-SS) were used to calculate students' academic burnout. Descriptive analysis, correlation analysis, hierarchical linear regression analysis and structural equation modeling were used to analyze the collected data. Results The results identified that in the context of online learning there was a positive correlation between medical students' stress and academic burnout, and their resilience played a partial mediating role. However, social support did not directly affect academic burnout, but inhibited the prevalence of academic burnout through resilience. In addition, stress was negatively related to resilience, while social support was positively related to resilience. Resilience was found to be negatively related to medical students' academic burnout in online learning. Conclusion The results of this study can provide a reference for the future development of appropriate educational strategies and coping measures to ameliorate the academic burnout of medical students.

15.
Elife ; 112022 05 19.
Article in English | MEDLINE | ID: covidwho-1939370

ABSTRACT

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of Bloc1s1 mRNA encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Inactivation of the Bloc1s1 gene impaired the ability to assemble BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Bloc1s1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus murine hepatitis virus also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.


Subject(s)
Brucella , Brucellosis , Animals , Brucellosis/metabolism , Brucellosis/microbiology , Endoribonucleases/metabolism , Endosomes/metabolism , Mice , Protein Serine-Threonine Kinases
16.
Int J Environ Res Public Health ; 19(10)2022 05 22.
Article in English | MEDLINE | ID: covidwho-1903372

ABSTRACT

During the COVID-19 pandemic, teachers had to conduct online classes because of the breakdown of school learning. Teacher competence has a great impact on the students' learning outcomes in online learning. Teacher resilience is also important to help teachers survive and achieve a high level of well-being in emergency situations. Previous studies have explored the protective and risk factors of teacher resilience, among which teacher competence in various aspects is included. In addition, teachers' age differences in competence and resilience have been the focus of past studies. However, few studies have investigated the impact of teacher competence on students' online learning outcomes, the mediating role of teacher resilience, and the moderating effect of age when teachers participate in emergent online teaching. To address the above gap, this study explored teachers' perceptions of students' online learning outcomes and how teacher competence in online teaching and resilience can predict these outcomes. The data of 159,203 participants were collected and subjected to correlation analyses and a moderated-mediation effect test. The results indicated that (1) teacher competence in online teaching was positively related to perceived online learning outcomes; (2) teacher resilience was positively related to the teachers' perceived online learning outcomes; (3) teacher resilience played a partial mediating role between teacher competence in online teaching and perceived online learning outcomes; and (4) teachers' age moderated the direct and indirect relation between teacher competence in online teaching and perceived online learning outcomes. The findings imply that teachers should strengthen their own teaching competence and their resilience before conducting online teaching. In addition, this study proposes intervention strategies to enhance teachers' resilience and well-being through teacher competence cultivation and provides suggestions for different age levels of teachers to develop and train their online teaching competence and resilience in the future.


Subject(s)
COVID-19 , Education, Distance , Educational Personnel , COVID-19/epidemiology , Disease Outbreaks , Humans , Pandemics
17.
Antioxidants (Basel) ; 11(5)2022 May 05.
Article in English | MEDLINE | ID: covidwho-1875461

ABSTRACT

Ivermectin (IVM) could cause potential neurotoxicity; however, the precise molecular mechanisms remain unclear. This study explores the cytotoxicity of IVM in human neuroblastoma (SH-SY5Y) cells and the underlying molecular mechanisms. The results show that IVM treatment (2.5-15 µM) for 24 h could induce dose-dependent cell death in SH-SY5Y cells. Compared to the control, IVM treatment significantly promoted the production of ROS, mitochondrial dysfunction, and cell apoptosis. IVM treatment also promoted mitophagy and autophagy, which were charactered by the decreased expression of phosphorylation (p)-Akt and p-mTOR proteins, increased expression of LC3II, Beclin1, ATG5, PINK, and Pakin1 proteins and autophagosome formation. N-acetylcysteine treatment significantly inhibited the IVM-induced production of ROS and cell death in SH-SY5Y cells. Autophagy inhibitor (e.g., 3-methyladenine) treatment significantly inhibited IVM-induced autophagy, oxidative stress, and cell apoptosis. Taken together, our results reveal that IVM could induce autophagy and apoptotic cell death in SH-SY5Y cells, which involved the production of ROS, activation of mitochondrial pathway, and inhibition of Akt/mTOR pathway. Autophagy inhibition improved IVM-induced oxidative stress and apoptotic cell death in SH-SY5Y cells. This current study provides new insights into understanding the molecular mechanism of IVM-induced neurotoxicity and facilitates the discovery of potential neuroprotective agents.

18.
J Virol ; 96(12): e0041222, 2022 06 22.
Article in English | MEDLINE | ID: covidwho-1874504

ABSTRACT

SARS-CoV-2 is the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19) and poses a significant threat to global health. N protein (NP), which is a major pathogenic protein among betacoronaviruses, binds to the viral RNA genome to allow viral genome packaging and viral particle release. Recent studies showed that NP antagonizes interferon (IFN) induction and mediates phase separation. Using live SARS-CoV-2 viruses, this study provides solid evidence showing that SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming G3BP1-mediated antiviral innate immunity. G3BP1 conditional knockout mice (g3bp1fl/fL, Sftpc-Cre) exhibit significantly higher lung viral loads after SARS-CoV-2 infection than wild-type mice. Our findings contribute to the growing body of knowledge regarding the pathogenicity of NPSARS-CoV-2 and provide insight into new therapeutics targeting NPSARS-CoV-2. IMPORTANCE In this study, by in vitro assay and live SARS-CoV-2 virus infection, we provide solid evidence that the SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming antiviral innate immunity mediated by G3BP1 in A549 cell lines and G3BP1 conditional knockout mice (g3bp1-cKO) mice, which provide in-depth evidence showing the mechanism underlying NP-related SARS-CoV-2 pathogenesis through G3BPs.


Subject(s)
COVID-19 , Coronavirus Nucleocapsid Proteins , Poly-ADP-Ribose Binding Proteins , SARS-CoV-2 , Virus Replication , Adaptor Proteins, Signal Transducing/metabolism , Animals , COVID-19/immunology , COVID-19/virology , Coronavirus Nucleocapsid Proteins/metabolism , DNA Helicases/metabolism , Host Microbial Interactions/immunology , Mice , Phosphoproteins/metabolism , Poly-ADP-Ribose Binding Proteins/metabolism , RNA Helicases/metabolism , RNA Recognition Motif Proteins/metabolism , RNA-Binding Proteins/metabolism , Stress Granules , Virus Replication/genetics
19.
Energies ; 15(10):3510, 2022.
Article in English | ProQuest Central | ID: covidwho-1870852

ABSTRACT

There has always been a complex relationship between uncertainty and crude oil prices. Three types of uncertainty, i.e., economic policy uncertainty, geopolitical risk uncertainty, and climate policy uncertainty (EPU, GPR, and CPU for short), have exacerbated abnormal fluctuations in the energy market, making crude oil prices volatile more and more frequently, especially from the perspective of the financial attribute of crude oil. Based on the time-series data related to uncertainties and crude oil prices from December 2001 to March 2021, this paper uses the quantile-on-quantile regression (QQR) method to explore the overall impact of various uncertainties on crude oil prices. Moreover, this paper adopts the QQR method based on the wavelet transform to investigate the heterogeneous effects of various uncertainties on crude oil prices at different time scales. The following conclusions are obtained. First, there are significant differences in the overall impact of the three types of uncertainties on crude oil prices, and this heterogeneity is reflected in quantiles of the peak impact intensity, the impact direction, and the fluctuation change. Second, the impact intensities of the three types of uncertainties on crude oil prices are significantly different at different time scales. This is mainly reflected in the different periods of significant impact of the three uncertainties on crude oil prices. Third, the impact directions and fluctuations of the three types of uncertainties on crude oil prices are heterogeneous at different time scales.

20.
Cell Rep ; 39(5): 110770, 2022 05 03.
Article in English | MEDLINE | ID: covidwho-1859379

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , Antibodies, Viral , Cryoelectron Microscopy , Humans , Immunoglobulin Fab Fragments , Spike Glycoprotein, Coronavirus
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