Harringtonine: A more effective antagonist for Omicron variant.

Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC50 of 0.217 µM, while the IC50 in delta variant decreased to 0.101 µM, the IC50 in Omicron BA.1 variant was 0.042 µM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC50 in Omicron BA.5 was even lower than 0.0019 µM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2.

Engineering highly efficient NIR-II FRET platform for Background-Free homogeneous detection of SARS-CoV-2 neutralizing antibodies in whole blood.

Förster or fluorescence resonance energy transfer (FRET) enables to probe biomolecular interactions, thus playing a vital role in bioassays. However, conventional FRET platforms suffer from limited sensitivity due to the low FRET efficiency and poor anti-interference of existing FRET pairs. Here we report a NIR-II (1000-1700 nm) FRET platform with extremely high FRET efficiency and exceptional anti-interference capability. This NIR-II FRET platform is established based on a pair of lanthanides downshifting nanoparticles (DSNPs) by employing Nd3+ doped DSNPs as an energy donor and Yb3+ doped DSNPs as an energy acceptor. The maximum FRET efficiency of this well-engineered NIR-II FRET platform reaches up to 92.2%, which is much higher than most commonly used ones. Owing to the all-NIR advantage (λex = 808 nm, λem = 1064 nm), this highly efficient NIR-II FRET platform exhibits extraordinary anti-interference in whole blood, and thus enabling background-free homogeneous detection of SARS-CoV-2 neutralizing antibodies in clinical whole blood sample with high sensitivity (limit of detection = 0.5 µg/mL) and specificity. This work opens up new opportunities for realizing highly sensitive detection of various biomarkers in biological samples with severe background interference.

Global age-structured spatial modeling for emerging infectious diseases like COVID-19.

Modeling the global dynamics of emerging infectious diseases (EIDs) like COVID-19 can provide important guidance in the preparation and mitigation of pandemic threats. While age-structured transmission models are widely used to simulate the evolution of EIDs, most of these studies focus on the analysis of specific countries and fail to characterize the spatial spread of EIDs across the world. Here, we developed a global pandemic simulator that integrates age-structured disease transmission models across 3,157 cities and explored its usage under several scenarios. We found that without mitigations, EIDs like COVID-19 are highly likely to cause profound global impacts. For pandemics seeded in most cities, the impacts are equally severe by the end of the first year. The result highlights the urgent need for strengthening global infectious disease monitoring capacity to provide early warnings of future outbreaks. Additionally, we found that the global mitigation efforts could be easily hampered if developed countries or countries near the seed origin take no control. The result indicates that successful pandemic mitigations require collective efforts across countries. The role of developed countries is vitally important as their passive responses may significantly impact other countries.

Mitochondria-Targeted Fluorescent Nanoparticles with Large Stokes Shift for Long-Term BioImaging.

Mitochondria (MITO) play a significant role in various physiological processes and are a key organelle associated with different human diseases including cancer, diabetes mellitus, atherosclerosis, Alzheimer's disease, etc. Thus, detecting the activity of MITO in real time is becoming more and more important. Herein, a novel class of amphiphilic aggregation-induced emission (AIE) active probe fluorescence (AC-QC nanoparticles) based on a quinoxalinone scaffold was developed for imaging MITO. AC-QC nanoparticles possess an excellent ability to monitor MITO in real-time. This probe demonstrated the following advantages: (1) lower cytotoxicity; (2) superior photostability; and (3) good performance in long-term imaging in vitro. Each result of these indicates that self-assembled AC-QC nanoparticles can be used as effective and promising MITO-targeted fluorescent probes.

Status of and perspectives on COVID-19 vaccination after lifting of the dynamic zero-COVID policy in China

Summary On December 7, 2022, China's National Health Commission issued the Ten New Covid Rules lifting the dynamic zero-COVID policy. In the interim, vaccination campaigns continue to be promoted. We assessed the potential impacts on the status, perceptions, and attitudes toward COVID-19 vaccines via an online self-administered questionnaire. Among 1,170 participants, 1,142 (97.6%) participants were vaccinated against COVID-19, and 51.8% (591/1,142) have already received the booster. More than half of the participants who were vaccinated were ages 31 to 50 (51.8%). Participants believed the following strategies could improve the vaccination rate: timely feedback of the vaccination data (such as safety, efficacy, and other issues of public concern) from authoritative media (95.6%), increasing the number of vaccination sites and availability of vaccines and using more convenient methods of making appointment (95.2%), recommendations from friends and relatives (94.8%), and presenting the qualifications of the staff performing vaccination (89.1%). More measures, including targeted measures for different age groups and timely feedback on the vaccination data including safety and efficacy from authoritative media, are likely to help improve vaccination rates.

TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.

Predicting compassion fatigue among psychological hotline counselors using machine learning techniques.

During the outbreak of coronavirus disease 2019, psychological hotline counselors frequently address help-seekers' traumatic experiences from time to time, which possibly causes counselors' compassion fatigue. The present study aimed to explore the predictors of compassion fatigue among a high-risk population of psychological hotline counselors. Seven hundred and twelve psychological hotline counselors were recruited from the Mental Health Service Platform at Central China Normal University, Ministry of Education, then were asked to complete the questionnaires measuring compassion fatigue, trait empathy, social support, trait mindfulness, counselor's self-efficacy, humor, life meaning, and post-traumatic growth. A chi-square test was utilized to filter for the top-20 predictive variables. Machine learning techniques, including logistic regression, decision tree, random forest, k-nearest neighbor, support vector machine, and naïve Bayes were employed to predict compassion fatigue. The results showed that the most important predictors of compassion fatigue were meaning in life, counselors' self-efficacy, mindfulness, and empathy. Except for the decision tree, the rest machine learning techniques obtained good performance. Naïve Bayes presented the highest area under the receiver operating characteristic curve of 0.803. Random forest achieved the least classification error of 23.64, followed by Naïve Bayes with a classification error of 23.85. These findings support the potential application of machine learning techniques in the prediction of compassion fatigue. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-021-01776-7.

Corrigendum: Delayed diagnosis and treatment of cancer patients during the COVID-19 pandemic in Henan, China: An interrupted time series analysis.

[This corrects the article DOI: 10.3389/fpubh.2022.881718.].

A Review of Filtration Performance of Protective Masks.

Masks are essential and effective small protective devices used to protect the general public against infections such as COVID-19. However, available systematic reviews and summaries on the filtration performance of masks are lacking. Therefore, in order to investigate the filtration performance of masks, filtration mechanisms, mask characteristics, and the relationships between influencing factors and protective performance were first analyzed through mask evaluations. The summary of filtration mechanisms and mask characteristics provides readers with a clear and easy-to-understand theoretical cognition. Then, a detailed analysis of influencing factors and the relationships between the influencing factors and filtration performance is presented in. The influence of the aerosol size and type on filtration performance is nonlinear and nonconstant, and filtration efficiency decreases with an increase in the gas flow rate; moreover, fitness plays a decisive role in the protective effects of masks. It is recommended that the public should wear surgical masks to prevent COVID-19 infection in low-risk and non-densely populated areas. Future research should focus on fitness tests, and the formulation of standards should also be accelerated. This paper provides a systematic review that will be helpful for the design of masks and public health in the future.

Immunological and metabolic characteristics of the Omicron variants infection.

The Omicron variants of SARS-CoV-2, primarily authenticated in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wildtype SARS-CoV-2. Omicron could hardly be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescents infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8 + T cell epitopes, compared with Delta. These epitopes could induce robust CD8 + T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8 + T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells. Consistently, a greater fraction of memory CD8 + T cells existed in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.

Interpretation bias in health anxiety: a systematic review and meta-analysis.

Interpretation bias (i.e. the selective negative interpretation of ambiguous stimuli) may contribute to the development and maintenance of health anxiety. However, the strength of the empirical evidence for this association remains a topic of debate. This study aimed to estimate the association between health anxiety and interpretation bias and to identify potential moderators of this association. Chinese-language databases (CNKI, VIP, and Wanfang), English-language databases (Web of Science, PubMed, PsycINFO, and Scopus), and German-language databases (Psyndex and PubPsych) were searched for relevant studies. There were 36 articles (39 studies) identified by this search (N = 8984), of which 32 articles (34 studies) were included in the meta-analysis (N = 8602). Results revealed a medium overall effect size (g = 0.67). Statistically equivalent effect sizes were observed for patients diagnosed with clinical health anxiety (g = 0.58) and subclinical health anxiety (g = 0.72). The effect sizes for threat stimuli that were health related (g = 0.68) and not health related (g = 0.63) did not differ significantly. The effect size for studies using an offline paradigm (g = 0.75) was significantly higher than that for studies using an online paradigm (g = 0.50). It is concluded that health anxiety is significantly and robustly associated with interpretation bias. These findings are of central importance for the advancement of models and treatment of health anxiety.

The biological responses of vitamin K2: A comprehensive review.

Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in the VitK family, found, respectively, in green leafy plants and algae (VitK1) and animal and fermented foods (VitK2). The present review explores the multiple biological functions of VitK2 from recently published in vitro and in vivo studies, including promotion of osteogenesis, prevention of calcification, relief of menopausal symptoms, enhancement of mitochondrial energy release, hepato- and neuro-protective effects, and possible use in treatment of coronavirus disease. The mechanisms of action associated with these biological effects are also explored. Overall, the findings presented here suggest that VitK, especially VitK2, is an important nutrient family for the normal functioning of human health. It acts on almost all major body systems and directly or indirectly participates in and regulates hundreds of physiological or pathological processes. However, as biological and clinical data are still inconsistent and conflicting, more in-depth investigations are warranted to elucidate its potential as a therapeutic strategy to prevent and treat a range of disease conditions.

Tissue-resident immunity in the lung: a first-line defense at the environmental interface.

The lung is a vital organ that incessantly faces external environmental challenges. Its homeostasis and unimpeded vital function are ensured by the respiratory epithelium working hand in hand with an intricate fine-tuned tissue-resident immune cell network. Lung tissue-resident immune cells span across the innate and adaptive immunity and protect from infectious agents but can also prove to be pathogenic if dysregulated. Here, we review the innate and adaptive immune cell subtypes comprising lung-resident immunity and discuss their ontogeny and role in distinct respiratory diseases. An improved understanding of the role of lung-resident immunity and how its function is dysregulated under pathological conditions can shed light on the pathogenesis of respiratory diseases.

Perceived stress and stress responses during COVID-19: The multiple mediating roles of coping style and resilience.

Although many studies have examined the effects of perceived stress on some specific stress responses during the COVID-19, a comprehensive study is still lacking. And the co-mediating role of coping style and resilience as important mediators of stress processes is also unclear. This study aimed to explore the effects of perceived stress on emotional, physical, and behavioral stress responses and the mediating roles of coping style and resilience in Chinese population during the recurrent outbreak of COVID-19 from a comprehensive perspective. 1087 participants were recruited to complete the anonymous online survey including the Perceived Stress Scale, the Stress Response Questionnaire, the Simplified Coping Style Questionnaire and the Emotional Resilience Questionnaire. Pearson's correlation and Hayes PROCESS macro 3.5 model 6 were used in the mediating effect analysis. Results showed that positive coping style and resilience both buffered the negative effects of perceived stress on emotional, physical, and behavioral responses through direct or indirect pathways, and resilience had the strongest mediating effects. The findings urged relevant authorities and individuals to take measures to promote positive coping style and resilience to combat the ongoing pandemic stress and protect public physical and mental health.

Discovery and Crystallographic Studies of Nonpeptidic Piperazine Derivatives as Covalent SARS-CoV-2 Main Protease Inhibitors.

The spread of SARS-CoV-2 keeps threatening human life and health, and small-molecule antivirals are in demand. The main protease (Mpro) is an effective and highly conserved target for anti-SARS-CoV-2 drug design. Herein, we report the discovery of potent covalent non-peptide-derived Mpro inhibitors. A series of covalent compounds with a piperazine scaffold containing different warheads were designed and synthesized. Among them, GD-9 was identified as the most potent compound with a significant enzymatic inhibition of Mpro (IC50 = 0.18 µM) and good antiviral potency against SARS-CoV-2 (EC50 = 2.64 µM), similar to that of remdesivir (EC50 = 2.27 µM). Additionally, GD-9 presented favorable target selectivity for SARS-CoV-2 Mpro versus human cysteine proteases. The X-ray co-crystal structure confirmed our original design concept showing that GD-9 covalently binds to the active site of Mpro. Our nonpeptidic covalent inhibitors provide a basis for the future development of more efficient COVID-19 therapeutics.

Lipid-mRNA nanoparticles landscape for cancer therapy.

Intracellular delivery of message RNA (mRNA) technique has ushered in a hopeful era with the successive authorization of two mRNA vaccines for the Coronavirus disease-19 (COVID-19) pandemic. A wide range of clinical studies are proceeding and will be initiated in the foreseeable future to treat and prevent cancers. However, efficient and non-toxic delivery of therapeutic mRNAs maintains the key limited step for their widespread applications in human beings. mRNA delivery systems are in urgent demand to resolve this difficulty. Recently lipid nanoparticles (LNPs) vehicles have prospered as powerful mRNA delivery tools, enabling their potential applications in malignant tumors via cancer immunotherapy and CRISPR/Cas9-based gene editing technique. This review discusses formulation components of mRNA-LNPs, summarizes the latest findings of mRNA cancer therapy, highlights challenges, and offers directions for more effective nanotherapeutics for cancer patients.

Social-Ecological Factors Predict College Students’ Physical Activities and Sedentary Behavior

Guided by the socio-ecological model, the aim of this study was to investigate the predictive strengths of individual, social, and physical environmental factors toward different intensities of physical activity (PA;vigorous PA, moderate PA, walking) and sedentary behavior (SB) among college students. A cross-sectional research design was used. There were 287 college students (Mage = 20.75 ± 2.91;54% female) recruited from a public research university in the Southwestern United States. Participants completed previously validated questionnaires assessing their PA, SB, and perceptions of self-efficacy, social support, and physical environment variables. Correlation and hierarchical regression analyses were performed to examine the associations and the relative contributions of those individual, social, and physical environmental factors to PA and SB, respectively. The findings indicated that self-efficacy, social support from friends, and convenience of using exercise facilities were positively correlated with vigorous PA. Self-efficacy and physical environmental factor such as convenience of using exercise facilities were significantly associated with students’ moderate PA. Physical environmental factors, including convenience of using exercise facilities, satisfaction with neighborhood services, ease of walking to public transportation stop, and detached single-family residence were significantly related to walking, while only detached single-family residence was associated to SB. The results highlight PA interventions may do well to focus on the promotion of individual and environmental variables to increase PA in college students. More evidence is needed to determine the relationships between social ecological factors and SB.

[Exploration and practice of the teaching system for "Human and Animal Physiology" in post pandemic era].

After the outbreak of COVID-19, the widespread application of online teaching has brought challenges and opportunities for higher education. Developing an effective teaching system is the focus of curriculum teaching reform in the post pandemic era. According to the characteristics of Human and Animal Physiology, the course teachers has developed a new teaching system by updating the teaching concept, reconstructing the contents of the course, changing the teaching modes, strengthening the integration of moral and intellectual education, and improving the assessment approaches. This teaching system is aimed at meeting the need of personalized learning for students and adapting to a new teaching environment. This article introduces the exploration and practice of the curriculum reform.

Attentional bias toward health-threat in health anxiety: a systematic review and three-level meta-analysis.

Attentional bias toward health-threat may theoretically contribute to the development and maintenance of health anxiety, but the empirical findings have been controversial. This study aimed to synthesize and explore the heterogeneity in a health-threat related attentional bias of health-anxious individuals, and to determine the theoretical model that better represents the pattern of attentional bias in health anxiety. Four databases (Web of Science, PubMed, PsycINFO, and Scopus) were searched for relevant studies, with 17 articles (N = 1546) included for a qualitative review and 16 articles (18 studies) for a three-level meta-analysis (N = 1490). The meta-analytic results indicated that the health anxiety group, compared to the control group, showed significantly greater attentional bias toward health-threat (g = 0.256). Further analyses revealed that attentional bias type, paradigm, and stimuli type were significant moderators. Additionally, compared to the controls, health-anxious individuals displayed significantly greater attention maintenance (g = 0.327) but nonsignificant attention vigilance to health-threat (g = -0.116). Our results provide evidence for the attention maintenance model in health-anxious individuals. The implications for further research and treatment of elevated health anxiety in the context of coronavirus disease-2019 (COVID-19) were also discussed.