Psychological distress and academic self-efficacy of nursing undergraduates under the normalization of COVID-19: multiple mediating roles of social support and mindfulness.

BACKGROUND: Nursing undergraduates' academic self-efficacy is a significant factor in determining their learning motivation, cognition, and emotions. It has a significant impact on improving academic performance and achieving learning goals. METHODS: To explore the mechanism of psychological distress affecting the academic self-efficacy of nursing undergraduates, the generalized anxiety disorder scale-7, patient health questionnaire-9, academic self-efficacy scale, perceived social support scale and mindful attention awareness scale were conducted. RESULTS: Model fitness indexes of the structural equation model is good (CMIN/DF = 1.404, RMSEA = 0.042, GFI = 0.977, IFI = 0.977, TLI = 0.954, CFI = 0.975, NFI = 0.923). Structural equation model analysis showed that social support and mindfulness were the mediating variables of psychological distress on academic self-efficacy. Mediating variables accounted for 44% of the total effect value (- 0.3) with a value of - 0.132. Three paths were verified: psychological distress indirectly affected academic self-efficacy through social support (- 0.064); psychological distress indirectly affected academic self-efficacy through mindfulness (- 0.053); psychological distress indirectly affected academic self-efficacy through social support and mindfulness (- 0.015). CONCLUSIONS: Social support and mindfulness play significant mediating roles in the effect of psychological distress on academic self-efficacy, and the chain mediating role of social support and mindfulness is also significant. Educators may mitigate the impact of psychological distress on academic self-efficacy by enhancing students' social support and mindfulness.

Relationship between Anxiety, Depression and Learning Burnout of Nursing Undergraduates after the COVID-19 Epidemic: The Mediating Role of Academic Self-Efficacy.

BACKGROUND: Although cross-sectional studies on the learning status of nursing undergraduates during the COVID-19 epidemic have surged, few studies have explored the normalization of COVID-19 on students' learning burnout and mental health. The study was designed to investigate the learning burnout of nursing undergraduates in school under the normalization of the COVID-19 epidemic and explore the hypothesized mediation effect of academic self-efficacy in the relationship between anxiety, depression and learning burnout in Chinese nursing undergraduates. METHODS: A cross-sectional study was conducted among nursing undergraduates in the school of nursing of a university in Jiangsu Province, China (n = 227). A general information questionnaire, College Students' Learning Burnout Questionnaire, Generalized Anxiety Disorder Scale (GAD-7), and Patient Health Questionnaire depression scale (PHQ-9) were administered. Descriptive statistical analysis, Pearson correlation analysis, and multiple linear regression analysis were performed via SPSS 26.0. Process plug-in (Model 4) was used to test the mediating effect of academic self-efficacy (bootstrap 5000 iterations, α = 0.05). RESULTS: Learning burnout (54.1 ± 0.656) was positively correlated with anxiety (4.6 ± 0.283) and depression (5.3 ± 0.366) (p < 0.01) and was negatively correlated with academic self-efficacy (74.41 ± 0.674) (p < 0.01). Academic self-efficacy plays a mediating role between anxiety and learning burnout (0.395/0.493, 80.12%) and a mediating role between depression and learning burnout (0.332/0.503, 66.00%). CONCLUSION: Academic self-efficacy has a significant predictive effect on learning burnout. Schools and teachers should strengthen the screening and counselling of students' psychological problems, detect learning burnout caused by emotional problems in advance and improve students' initiative and enthusiasm for learning.

Evaluating Whether and How Public Health Event Information Frameworks Promote Pro-Environmental Behavior.

The major public health emergencies (PHEs) represented by the COVID-19 pandemic, while posing a serious threat to human health, have led people to rethink about the harmonious relationship between humans and nature. It is worthy to explore whether and how the framework effect of event information can be used to turn crises into opportunities to promote public pro-environmental behavior (PEB). Through a pre-and post-test control experiment, this study took the COVID-19 pandemic as a case, to explore the effects of four PHE information frameworks on promoting PEB, coupled with two information loss-gain frameworks and two information content frameworks. The results showed that all four information frameworks contribute to the public PEB. However, there are differences: only the environmental gain information effect is significant for PEB in the private sphere. The environmental loss and health gain information are effective for PEB in organizations. However, in the public sphere, all four information frameworks significantly motivate PEB. Further factorial analysis revealed that the interaction between the information content and loss-gain framework was not significant, with the latter playing the dominant role. These findings provide a new approach to how to develop the information framework effect and turn crises into opportunities to promote public PEB in the context of major PHEs.

In vitro and in vivo effects of 3-indoleacetonitrile-A potential new broad-spectrum therapeutic agent for SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has resulted in significant global morbidity, mortality, and societal disruption. Currently, effective antiviral drugs for the treatment of SARS-CoV-2 infection are limited. Therefore, safe and effective antiviral drugs to combat COVID-19 are urgently required. In previous studies, we showed that 3-indoleacetonitrile, a plant growth hormone produced by cruciferous (Brassica) vegetables, is effective in treating influenza A virus infection. However, the molecular mechanisms underlying these effects remain unclear. Herein, we demonstrated that 3-indoleacetonitrile exhibits broad-spectrum antiviral activity and is effective against HSV-1 and VSV infections in vitro. This phenomenon prompted us to study its role in the anti-SARS-CoV-2 process. Interestingly, 3-indoleacetonitrile exhibited antiviral activity against SARS-CoV-2 in vitro. Importantly, tail vein injection of 3-indoleacetonitrile resulted in good antiviral activity in mouse models infected with WBP-1 (a mouse adaptation of the SARS-CoV-2 strain). Mechanistically, 3-indoleacetonitrile promoted the host interferon signalling pathway response and inhibited autophagic flux. Furthermore, we demonstrated that 3-indoleacetonitrile induced an increase in mitochondrial antiviral-signalling (MAVS) protein levels, which might be attributed to its inhibition of the interaction between MAVS and the selective autophagy receptor SQSTM1. Overall, our results demonstrate that 3-indoleacetonitrile is potently active against SARS-CoV-2 in vitro and in vivo, which may provide a foundation for further clinical testing for the treatment of COVID-19. In addition, considering its broad-spectrum antiviral effect, it should be explored whether it also has an effect on other viruses that threaten human health.

Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Scutellariae radix (“Huang-Qin” in Chinese) is a well-known traditional herbal medicine and popular dietary supplement in the world, extensively used in prescriptions of TCMs as adjuvant treatments for coronavirus pneumonia 2019 (COVID-19) patients in China. According to the differences in its appearance, Scutellariae radix can be classified into two kinds: ZiQin (1∼3 year-old Scutellariae baicalensis with hard roots) and KuQin (more than 3 year-old S. baicalensis with withered pithy roots). In accordance with the clinical theory of TCM, KuQin is superior to ZiQin in cooling down the heat in the lung. However, the potential active ingredients and underlying mechanisms of Scutellariae radix for the treatment of COVID-19 remain largely unexplored. It is still not clear whether there is a difference in the curative effect of ZiQin and KuQin for the treatment of COVID-19. In this research, network pharmacology, LC-MS based plant metabolomics, and in vitro bioassays were integrated to explore both the potential active components and mechanism of Scutellariae radix for the treatment of COVID-19. As the results, network pharmacology combined with molecular docking analysis indicated that Scutellariae radix primarily regulates the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin, and blocks SARS-CoV-2 spike binding to human ACE2 receptors. In vitro bioassays showed that baicalein and scutellarein exhibited more potent anti-inflammatory and anti-infectious effects than baicalin, the component with the highest content in Scutellariae radix. Moreover, baicalein inhibited SARS-CoV-2’s entry into Vero E6 cells with an IC50 value of 142.50 μM in a plaque formation assay. Taken together, baicalein was considered to be the most crucial active component of Scutellariae radix for the treatment of COVID-19 by integrative analysis. In addition, our bioassay study revealed that KuQin outperforms ZiQin in the treatment of COVID-19. Meanwhile, plant metabolomics revealed that baicalein was the compound with the most significant increase in KuQin compared to ZiQin, implying the primary reason for the superiority of KuQin over ZiQin in the treatment of COVID-19.

Automated Multi-View Multi-Modal Assessment of COVID-19 Patients Using Reciprocal Attention and Biomedical Transform.

Automated severity assessment of coronavirus disease 2019 (COVID-19) patients can help rationally allocate medical resources and improve patients' survival rates. The existing methods conduct severity assessment tasks mainly on a unitary modal and single view, which is appropriate to exclude potential interactive information. To tackle the problem, in this paper, we propose a multi-view multi-modal model to automatically assess the severity of COVID-19 patients based on deep learning. The proposed model receives multi-view ultrasound images and biomedical indices of patients and generates comprehensive features for assessment tasks. Also, we propose a reciprocal attention module to acquire the underlying interactions between multi-view ultrasound data. Moreover, we propose biomedical transform module to integrate biomedical data with ultrasound data to produce multi-modal features. The proposed model is trained and tested on compound datasets, and it yields 92.75% for accuracy and 80.95% for recall, which is the best performance compared to other state-of-the-art methods. Further ablation experiments and discussions conformably indicate the feasibility and advancement of the proposed model.

Effects of Cell Phone Dependence on Mental Health Among College Students During the Pandemic of COVID-19: A Cross-Sectional Survey of a Medical University in Shanghai.

Objective: To investigate the effects of cell phone dependence (CPD) on mental health among undergraduates during the COVID-19 pandemic and further identify the determinants that may affect their mental health in China. Methods: The data were collected from 602 students at a medical school in Shanghai via an online survey conducted from December 2021 to February 2022. The Mobile Phone Addiction Index (MPAI) and Depression Anxiety Stress Scale (DASS) were applied to evaluate CPD and mental health, respectively. Independent sample t-test and one-way analysis of variance (ANOVA) were employed to compare the means of continuous variables among categorical groups. Correlations between continuous variables were detected using Pearson's correlation analysis. Univariable and multivariable logistic regressions were employed to identify the determinants of mental health. Results: Among the 402 eligible students, 73.88% were women with an average age of 20.19 ± 2.36 years. On average, the DASS score was 32.20 ± 11.07, the CPD score was 36.23 ± 11.89, and the cell phone use duration was 7.67 ± 3.61 h/day. CPD was found to have a negative effect on mental health among college students in Shanghai. Additionally, cell phone use duration, age, being senior students, faculty-student relationship, insomnia, tobacco use, obesity, and life satisfaction were clarified as contributing factors to mental health among college students. Conclusion: High degree of CPD could have a negative effect on college students' mental health, which might lead to some psychological problems. Appropriate actions and effective interventions are highly needed to prevent severe psychological injuries among college students in China.

Automated Multi-View Multi-Modal Assessment of COVID-19 Patients Using Reciprocal Attention and Biomedical Transform

Automated severity assessment of coronavirus disease 2019 (COVID-19) patients can help rationally allocate medical resources and improve patients' survival rates. The existing methods conduct severity assessment tasks mainly on a unitary modal and single view, which is appropriate to exclude potential interactive information. To tackle the problem, in this paper, we propose a multi-view multi-modal model to automatically assess the severity of COVID-19 patients based on deep learning. The proposed model receives multi-view ultrasound images and biomedical indices of patients and generates comprehensive features for assessment tasks. Also, we propose a reciprocal attention module to acquire the underlying interactions between multi-view ultrasound data. Moreover, we propose biomedical transform module to integrate biomedical data with ultrasound data to produce multi-modal features. The proposed model is trained and tested on compound datasets, and it yields 92.75% for accuracy and 80.95% for recall, which is the best performance compared to other state-of-the-art methods. Further ablation experiments and discussions conformably indicate the feasibility and advancement of the proposed model.

Discovery of honokiol thioethers containing 1,3,4-oxadiazole moieties as potential α-glucosidase and SARS-CoV-2 entry inhibitors.

Honokiol, isolated from a traditional Chinese medicine (TCM) Magnolia officinalis, is a biphenolic compound with several biological activities. To improve and broaden its biological activity, herein, two series of honokiol thioethers bearing 1,3,4-oxadiazole moieties were prepared and assessed for their α-glucosidase and SARS-CoV-2 entry inhibitory activities. Among all the honokiol thioethers, compound 7l exhibited the strongest α-glucosidase inhibitory effect with an IC50 value of 18.9 ± 2.3 µM, which was superior to the reference drug acarbose (IC50 = 24.4 ± 0.3 µM). Some interesting results of structure-activity relationships (SARs) have also been discussed. Enzyme kinetic study demonstrated that 7l was a noncompetitive α-glucosidase inhibitor, which was further supported by the results of molecular docking. Moreover, honokiol thioethers 7e, 9a, 9e, and 9r exhibited potent antiviral activity against SARS-CoV-2 pseudovirus entering into HEK-293 T-ACE2h. Especially 9a displayed the strongest inhibitory activity against SARS-CoV-2 pseudovirus entry with an IC50 value of 16.96 ± 2.45 µM, which was lower than the positive control Evans blue (21.98 ± 1.98 µM). Biolayer interferometry (BLI) binding and docking studies suggested that 9a and 9r may effectively block the binding of SARS-CoV-2 to the host ACE2 receptor through dual recognition of SARS-CoV-2 spike RBD and human ACE2. Additionally, the potent honokiol thioethers 7l, 9a, and 9r displayed relatively no cytotoxicity to normal cells (LO2). These findings will provide a theoretical basis for the discovery of honokiol derivatives as potential both α-glucosidase and SARS-CoV-2 entry inhibitors.

Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS.

Acute kidney injury (AKI) is a common complication among patients with the novel coronavirus (COVID-19). COVID-19 along with AKI usually resulted in a poor prognosis for those affected. Remdesivir is a novel antiviral drug that was urgently approved for the treatment of COVID-19. In the current study, safety data of remdesivir were limited. We gathered information on COVID-19 cases in patients with adverse events that were reported to the U.S. Food and Drug Administration (US FDA) Adverse Event Reporting System (FAERS) database. We employed the reporting odds ratio (ROR) method to perform disproportionality analysis. Finally, we identified 12,869 COVID-19 cases. A total of 3,991 of these cases reported remdesivir as a primary suspected drug, while 8,878 cases were treated with other drugs. More AKI events occurred in cases of male patients and those above the age of 65 years. We detected a significant association between remdesivir and AKI: ROR = 2.81, 95% CI (2.48, 3.18). The association was stronger after the propensity score matching ROR = 3.85, 95% CI (3.11, 4.78). The mean time to AKI event onset was 4.91 ± 7.25 days in COVID-19 cases with remdesivir therapy. The fatality proportion was 36.45% in AKI cases with remdesivir treatment. This pharmacovigilance study identified a significant association between AKI events and remdesivir treatment in COVID-19 patients by mining FAERS real-world big data. Although causality was not confirmed, the association between remdesivir and AKI should not be ignored, especially in the older, male COVID-19 inpatients.

Flight to Safety: How Economic Downturns Affect Talent Flows to Startups

Using proprietary data from AngelList Talent, we study how individuals’ job search and application behavior changed during the COVID downturn. We find that job seekers shifted their searches toward more established firms and away from early-stage startups, even within the same individual over time. Simultaneously, they broadened their other search parameters. Relative to more established firms, early-stage startups experienced a decline in applications, primarily driven by higher quality candidates. These declines hold within a firm or job posting over time. Our findings uncover a flight to safety channel in the labor market, which may amplify the pro-cyclical nature of entrepreneurial activities.

Prevalence and trend of low vision among primary and secondary school students in Wuhan from 2019 to 2020

Objective: To provide a large-scale assessment the prevalence of poor vision in 2020 among children and adolescents in Wuhan City, Hubei province and to provide basis for healthy vision promotion.

Gender Bias and the Lack of Equity in Pandemic Nursing in China: A Qualitative Study.

There has long been a gender bias in medicine. This qualitative study aims to identify the experience of sexism among frontline female nurses and further explore their expectations and possible strategies to get rid of gender bias. This is a descriptive phenomenological study of 23 female nurses with 11 ± 3.98 years of experience who spent 36 ± 6.50 days at the frontline during the initial COVID-19 outbreak. We employed Colaizzi's phenomenological analysis method to understand the subjective experiences, revealing the following themes: (a) materialization of gender identity; (b) incoordinate relationships; (c) future voice of female nurses. The gender bias experienced by female frontline nurses further challenges their emotional identity and self-identity. Therefore, it is important to require extensive consciousness-raising and policy support to defend female nurses' rights.

COVID-19 and Tuberculosis Coinfection: An Overview of Case Reports/Case Series and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases. Methods: The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro. Results: Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) (p < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5-16.73] vs. 8.015 [4.8-8.97] × 109/L) than survivors (p < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) (P < 0.01), respectively. Conclusion: In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.

Synthesis and Biological Evaluation of Honokiol Derivatives Bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones as Potential Viral Entry Inhibitors against SARS-CoV-2.

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD's binding with ACE2. Importantly, 6a and 6p (TC50 > 100 µM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 µM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p's antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.

SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced inflammatory responses are largely responsible for the death of novel coronavirus disease 2019 (COVID-19) patients. However, the mechanism by which SARS-CoV-2 triggers inflammatory responses remains unclear. Here, we aimed to explore the regulatory role of SARS-CoV-2 spike protein in infected cells and attempted to elucidate the molecular mechanism of SARS-CoV-2-induced inflammation. METHODS: SARS-CoV-2 spike pseudovirions (SCV-2-S) were generated using the spike-expressing virus packaging system. Western blot, mCherry-GFP-LC3 labeling, immunofluorescence, and RNA-seq were performed to examine the regulatory mechanism of SCV-2-S in autophagic response. The effects of SCV-2-S on apoptosis were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Western blot, and flow cytometry analysis. Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the mechanism of SCV-2-S in inflammatory responses. RESULTS: Angiotensin-converting enzyme 2 (ACE2)-mediated SCV-2-S infection induced autophagy and apoptosis in human bronchial epithelial and microvascular endothelial cells. Mechanistically, SCV-2-S inhibited the PI3K/AKT/mTOR pathway by upregulating intracellular reactive oxygen species (ROS) levels, thus promoting the autophagic response. Ultimately, SCV-2-S-induced autophagy triggered inflammatory responses and apoptosis in infected cells. These findings not only improve our understanding of the mechanism underlying SARS-CoV-2 infection-induced pathogenic inflammation but also have important implications for developing anti-inflammatory therapies, such as ROS and autophagy inhibitors, for COVID-19 patients.

Neural connectome prospectively encodes the risk of post-traumatic stress disorder (PTSD) symptom during the COVID-19 pandemic.

BACKGROUND: The novel coronavirus (COVID-19) pandemic has affected humans worldwide and led to unprecedented stress and mortality. Detrimental effects of the pandemic on mental health, including risk of post-traumatic stress disorder (PTSD), have become an increasing concern. The identification of prospective neurobiological vulnerability markers for developing PTSD symptom during the pandemic is thus of high importance. METHODS: Before the COVID-19 outbreak (September 20, 2019-January 11, 2020), some healthy participants underwent resting-state functional connectivity MRI (rs-fcMRI) acquisition. We assessed the PTSD symptomology of these individuals during the peak of COVID-19 pandemic (February 21, 2020-February 28, 2020) in China. This pseudo-prospective cohort design allowed us to test whether the pre-pandemic neural connectome status could predict the risk of developing PTSD symptom during the pandemic. RESULTS: A total of 5.60% of participants (n = 42) were identified as being high-risk to develop PTSD symptom and 12.00% (n = 90) exhibited critical levels of PTSD symptoms during the COVID-19 pandemic. Pre-pandemic measures of functional connectivity (the neural connectome) prospectively classified those with heightened risk to develop PTSD symptom from matched controls (Accuracy = 76.19%, Sensitivity = 80.95%, Specificity = 71.43%). The trained classifier generalized to an independent sample. Continuous prediction models revealed that the same connectome could accurately predict the severity of PTSD symptoms within individuals (r 2 = 0.31p<.0). CONCLUSIONS: This study confirms COVID-19 break as a crucial stressor to bring risks developing PTSD symptom and demonstrates that brain functional markers can prospectively identify individuals at risk to develop PTSD symptom.

Chemosensory Dysfunction Induced by Environmental Pollutants and Its Potential As a Novel Neurotoxicological Indicator: A Review.

Air pollution composed of the complex interactions among particular matter, chemicals, and pathogens is an emerging and global environmental issue that closely correlates with a variety of diseases and adverse health effects, especially increasing incidences of neurodegenerative diseases. However, as one of the prevalent health outcomes of air pollution, chemosensory dysfunction has not attracted enough concern until recently. During the COVID-19 pandemic, multiple scientific studies emphasized the plausibly essential roles of the chemosensory system in the airborne transmission airway of viruses into the human body, which can also be utilized by pollutants. In this Review, in addition to summarizing current progress regarding the contributions of traditional air pollutants to chemosensory dysfunction, we highlight the roles of emerging contaminants. We not only sum up clarified mechanisms, such as inflammation and apoptosis but also discuss some not yet completely identified mechanisms, e.g., disruption of olfactory signal transduction. Although the existing evidence is not overwhelming, the chemosensory system is expected to be a useful indicator in neurotoxicology and neural diseases based on accumulating studies that continually excavate the deep link between chemosensory dysfunction and neurodegenerative diseases. Finally, we argue the importance of studies concerning chemosensory dysfunction in understanding the health effects of air pollution and provide comments for some future directions of relevant research.

One-year follow-up of chest CT findings in patients after SARS-CoV-2 infection.

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.

Preliminary safety, tolerability and efficacy results of KN026 in combination with KN046 in patients with HER2 aberrated solid tumors

BackgroundHER2 potently inhibits innate immunity through cGAS–STING signaling,1 Meanwhile HER2 antibody induced ADCP will also lead to macrophage mediated immune suppression. Both preclinical and clinical studies have suggested a coordination of engagement of innate and adaptive immunity with the combination of an anti-HER2 antibody and an immune checkpoint blockade. KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86. Here we reported the interim results from an ongoing phase Ib dose escalation and expansion study assessing the safety, tolerability and preliminary efficacy for KN026 in combination with KN046 in Patients with HER2 aberrated solid tumors.MethodsThis study enrolled pts with solid tumors who failed available standard of care, HER2 aberration status confirmed locally (HER2 mutation, HER2 amplification and/or HER2 overexpression). Eligible pts received combination of KN026 and KN046 at three dose levels until disease progression, unacceptable toxicity or withdrawal of informed consent (DL1: KN026 20 mg/kg Q2W + KN046 3 mg/kg Q2W;DL2: KN026 20 mg/kg Q2W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W;DL3: KN026 30 mg/kg Q3W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W). Tumor response was evaluated Q8W per RECIST 1.1. Primary endpoint was DLT and key secondary endpoints were efficacy parameters (ORR, DOR, PFS).ResultsAs of the Sep. 08, 2020, 25 pts were enrolled into DL1 (n = 20, 3 for dose escalation), DL2 (n = 3) and DL3 (n = 2) (mGC/GEJ 15 pts;mCRC 8 pts;other solid tumors 2 pts). 15 pts remained on the study treatment and 10 pts discontinued treatment due to disease progression (n=5), death (n=2) and other reasons (n=3). 18 pts had HER2-positive status (12 of 18 failed previous trastuzumab therapy), 2 pts had HER2 mutation and 5 pts had HER2 low expression (without FISH amplification). No DLTs were observed. No pts experienced LVEF decreased or other clinically meaningful cardiac AEs. Treatment-related TEAEs occurred in 23 (92%) pts, of which 6 (24%) pts experienced grade 3 or above treatment-related TEAEs. 11 (44%) pts experienced irAEs, majority were of grade 1 or 2 except that 1 patient experienced grade 3 immune-mediated endocrinopathy. The most common (frequency ≥ 15%) KN026 or KN046 related TEAEs were infusion related reaction (n=11, 44.0%), anaemia (n=9, 36.0%), white blood cell count decreased (n=6, 24.0%), diarrhea (n=5, 20.0%), AST increased (n=5, 20.0%), platelet count decreased (n=5, 20.0%), rash (n=5, 20.0%) and ALT increased (n=4, 16.0%). The objective response rate in pts with HER2-positive tumors (n = 14 efficacy evaluable pts) was 9/14 (64.3%, 95% CI 35.1~87.2%) and disease control rate 13/14 (92.9%, 95% CI 66.1~99.8%). 4 out of 5 pts with HER2 mutation or low expression achieved SD including one patient with SD for more than 24 weeks. 2 death cases due to disease progression were reported, both only received one cycle of KN026 plus KN046 due to COVID-19 restriction.ConclusionsKN026 combined with KN046 is well tolerated and has demonstrated preliminary albeit profound anti-tumor activity in HER2-positive solid tumors.Trial RegistrationClinical trial information: NCT04040699ReferenceShiying Wu, Qian Zhang, Fei Zhang, et al. HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. Nature Cell Biology 2019;21:1027–1040.