Enantioselective Effect of Chiral Small Molecules in SARS-CoV-2 Vaccine-Induced Immune Response.

Although numerous chiral small molecules have been discovered and synthesized, the investigation on their enantioselective immunological effects remains limited. In this study, we designed and synthesized a pair of small molecule enantiomers (R/S-ResP) by covalently bonding two immunostimulators (resiquimod/Res) onto a planar chiral framework (paracyclophane/P). Notably, we found that S-ResP exhibits a 4.05-fold higher affinity for toll-like receptor 7 (TLR7) than R-ResP, thereby more effectively enhancing the functions of dendritic cells and macrophages in cytokine secretion and antigen internalization. Furthermore, we observed that S-ResP significantly enhances RBD antigen-induced cross-neutralization against various SARS-CoV-2 strains compared to R-ResP. These findings demonstrate the enantioselective effects of small molecules on regulating vaccine-induced immune responses and emphasize the significance of chirality in designing small molecular adjuvants.

China's Largest City-Wide Lockdown: How Extensively Did Shanghai COVID-19 Affect Intensity of Human Activities in the Yangtze River Delta?

COVID-19 has been the most widespread and far-reaching public health emergency since the beginning of the 21st century. The Chinese COVID-19 lockdown has been the most comprehensive and strict in the world. Based on the Shanghai COVID-19 outbreak in 2022, we analyzed the heterogeneous impact of the COVID-19 lockdown on human activities and urban economy using monthly nighttime light data. We found that the impact of lockdown on human activities in the Yangtze River Delta is very obvious. The number of counties in Shanghai, Jiangsu, Zhejiang and Anhui showing a downward trend of MNLR (Mean of Nighttime Light Radiation) is 100%, 97%, 99% and 85%, respectively. Before the outbreak of COVID-19, the proportion of counties with a downward trend of MNLR was 19%, 67%, 22% and 33%, respectively. Although the MNLR of some counties also decreased in 2019, the scope and intensity was far less than 2022. Under regular containment (2020 and 2021), MNLR in the Yangtze River Delta also showed a significant increase (MNLR change > 0). According to NLRI (Nighttime Light Radiation Influence), the Shanghai lockdown has significantly affected the surrounding provinces (Average NLRI < 0). Jiangsu is the most affected province other than Shanghai. At the same time, Chengdu-Chongqing, Guangdong–Hong Kong–Macao and the Triangle of Central China have no obvious linkage effect.

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.

BACKGROUND: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies. METHODS: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA. Patients aged 18 or older with previously treated B-cell malignancies (chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström macroglobulinaemia, or marginal zone lymphoma) who became intolerant of ibrutinib, acalabrutinib, or both, were orally administered zanubrutinib 160 mg twice daily or 320 mg once daily per investigator. The primary endpoint was recurrence and change in severity of ibrutinib or acalabrutinib intolerance events based on investigator-assessed adverse events. Secondary endpoints were investigator-assessed overall response rate; duration of response; disease control rate; and progression-free survival. Analyses included all patients who received any dose of the study drug. This study is registered with ClinicalTrials.gov, NCT04116437. FINDINGS: Between Oct 14, 2019, and Sept 8, 2021, 67 patients (36 [54%] men and 31 [46%] women) who were intolerant of ibrutinib (n=57; cohort 1) or of acalabrutinib or acalabrutinib and ibrutinib (n=10; cohort 2) were enrolled. 63 (94%) patients were White, one (2%) had multiple ethnicities, and three (5%) had unreported or unknown ethnicity. Most intolerance events (81 [70%] of 115 for ibrutinib; 15 [83%] of 18 for acalabrutinib) did not recur with zanubrutinib. Of the recurring events, seven (21%) of 34 ibrutinib intolerance events and two (67%) of three acalabrutinib intolerance events recurred at the same severity with zanubrutinib; 27 (79%) ibrutinib intolerance events and one (33%) acalabrutinib intolerance event recurred at a lower severity with zanubrutinib. No events recurred at higher severity. No grade 4 intolerance events recurred. 64 (96%) of 67 patients had one or more adverse events with zanubrutinib; the most common adverse events were contusion (in 15 [22%] of 67 patients), fatigue (14 [21%]), myalgia (ten [15%]), arthralgia (nine [13%]), and diarrhoea (nine [13%]). Atrial fibrillation occurred in three (4%) patients (all grade 2). Eight (12%) of 67 patients had serious adverse events (anaemia, atrial fibrillation, bronchitis, COVID-19, COVID-19 pneumonia, febrile neutropenia, salmonella gastroenteritis, transfusion reaction, trigeminal nerve disorder, and urinary tract infection). No treatment-related deaths occurred. The median follow-up time was 12·0 months (IQR 8·2-15·6). Among the 64 efficacy-evaluable patients, disease control rate was 93·8% (60; 95% CI 84·8-98·3) and overall response rate was 64·1% (41; 95% CI 51·1-75·7). The median duration of response was not reached; the 12-month event-free duration of response rate was 95·0% (95% CI 69·5-99·3). Similarly, median progression-free survival was not reached; 18-month progression-free survival was 83·8% (95% CI 62·6-93·6). INTERPRETATION: Patients intolerant of previous BTK inhibitors have limited treatment options. These results suggest that zanubrutinib, a safe and viable treatment for patients with B-cell malignancies, might fill that unmet need for those who exhibit intolerance to ibrutinib or acalabrutinib. FUNDING: BeiGene.

Bioinformatic analysis and preliminary validation of potential therapeutic targets for COVID-19 infection in asthma patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 19 (COVID-19). The number of confirmed cases of COVID-19 is also rapidly increasing worldwide, posing a significant challenge to human safety. Asthma is a risk factor for COVID-19, but the underlying molecular mechanisms of the asthma-COVID-19 interaction remain unclear. METHODS: We used transcriptome analysis to discover molecular biomarkers common to asthma and COVID-19. Gene Expression Omnibus database RNA-seq datasets (GSE195599 and GSE196822) were used to identify differentially expressed genes (DEGs) in asthma and COVID-19 patients. After intersecting the differentially expressed mRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify the common pathogenic molecular mechanism. Bioinformatic methods were used to construct protein-protein interaction (PPI) networks and identify key genes from the networks. An online database was used to predict interactions between transcription factors and key genes. The differentially expressed long noncoding RNAs (lncRNAs) in the GSE195599 and GSE196822 datasets were intersected to construct a competing endogenous RNA (ceRNA) regulatory network. Interaction networks were constructed for key genes with RNA-binding proteins (RBPs) and oxidative stress-related proteins. The diagnostic efficacy of key genes in COVID-19 was verified with the GSE171110 dataset. The differential expression of key genes in asthma was verified with the GSE69683 dataset. An asthma cell model was established with interleukins (IL-4, IL-13 and IL-17A) and transfected with siRNA-CXCR1. The role of CXCR1 in asthma development was preliminarily confirmed. RESULTS: By intersecting the differentially expressed genes for COVID-19 and asthma, 393 common DEGs were obtained. GO and KEGG enrichment analyses of the DEGs showed that they mainly affected inflammation-, cytokine- and immune-related functions and inflammation-related signaling pathways. By analyzing the PPI network, we obtained 10 key genes: TLR4, TLR2, MMP9, EGF, HCK, FCGR2A, SELP, NFKBIA, CXCR1, and SELL. By intersecting the differentially expressed lncRNAs for COVID-19 and asthma, 13 common differentially expressed lncRNAs were obtained. LncRNAs that regulated microRNAs (miRNAs) were mainly concentrated in intercellular signal transduction, apoptosis, immunity and other related functional pathways. The ceRNA network suggested that there were a variety of regulatory miRNAs and lncRNAs upstream of the key genes. The key genes could also bind a variety of RBPs and oxidative stress-related genes. The key genes also had good diagnostic value in the verification set. In the validation set, the expression of key genes was statistically significant in both the COVID-19 group and the asthma group compared with the healthy control group. CXCR1 expression was upregulated in asthma cell models, and interference with CXCR1 expression significantly reduced cell viability. CONCLUSIONS: Key genes may become diagnostic and predictive biomarkers of outcomes in COVID-19 and asthma. Video Abstract.

Identification of the Hub Genes and the Signaling Pathways in Human iPSC-Cardiomyocytes Infected by SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is an enveloped single-stranded RNA virus that can lead to respiratory symptoms and damage many organs such as heart, kidney, intestine, brain and liver. It has not been clearly documented whether myocardial injury is caused by direct infection of cardiomyocytes, lung injury, or other unknown mechanisms. The gene expression profile of GSE150392 was obtained from the Gene Expression Omnibus (GEO) database. The processing of high-throughput sequencing data and the screening of differentially expressed genes (DEGs) were implemented by R software. The R software was employed to analyze the Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was constructed by the STRING website. The Cytoscape software was applied for the visualization of PPI network and the identification of hub genes. The statistical analysis was performed by the GraphPad Prism software to verify the hub genes. A total of 516 up-regulated genes and 191 down-regulated genes were screened out. The top 1 enrichment items of GO in biological process (BP), Cellular Component (CC), and Molecular Function (MF) were type I interferon signaling pathway, sarcomere, and receptor ligand activity, respectively. The top 10 enrichment pathways, including TNF signaling pathway, were identified by KEGG enrichment analysis. A PPI network was established, consisting of 613 nodes and 3,993 edges. The 12 hub genes were confirmed as statistically significant, which was verified by GSE151879 dataset. In conclusion, the hub genes of human iPSC-cardiomyocytes infected with SARS-CoV-2 were identified through bioinformatics analysis, which may be used as biomarkers for further research.

An integrated fluorescent lateral flow assay for multiplex point-of-care detection of four respiratory viruses.

This work established a highly sensitive and specific quantum dot nanobeads-based lateral flow assay for multiplex detection of four respiratory virus markers at point of care. The respiratory virus antigens were detected by fluorescent lateral flow strips within 20 min. The limits of detection for SARS-CoV-2 antigen, IAV antigen, IBV antigen, and ADV antigen were 0.01 ng/mL, 0.05 ng/mL, 0.31 ng/mL, and 0.40 ng/mL, respectively, which were superior to that of conventional AuNPs-based colorimetric lateral flow assay. The coefficients of variation of the test strip were 6.09%, 2.24%, 7.92%, and 12.43% for these four antigens, which indicated that the proposed method had good repeatability. The specificity of the detection system was verified by different combinations of these four respiratory viruses and several other respiratory pathogens. These results indicated that this method could simultaneously detect SARS-CoV-2, IAV, IBV and ADV in a short assay time, showing the remarkable potential for the rapid and multiplex detection of respiratory viruses in resource-limited settings.

Association between fear of COVID-19 and hoarding behavior during the outbreak of the COVID-19 pandemic: The mediating role of mental health status

Hoarding behavior can effectively improve people's ability to resist risks, so as to reduce the negative effects of risks. However, excessive hoarding behavior will seriously reduce people's quality of life. The COVID-19 pandemic can cause excessive hoarding in a large number of people in a short period of time, and also cause a series of economic problems such as social material shortage. It is unclear how hoarding levels are linked to fear and negative emotions caused by COVID-19 among people of different educational backgrounds and social status. The purpose of this study was to explore the relationship between fear of COVID-19 and hoarding behavior in different populations in school and social contexts, as well as the mediating role of negative emotions and the moderating role of subjective/objective social status and education level in this process. An online cross-sectional survey was conducted in various provinces in China in January 2022. Demographic information, the MacArthur Scale of Subjective Social Status, the Fear of COVID-19 scale, the Depression Anxiety Stress-21, and the Saving Inventory-Revised were used to evaluate the severity of individual hoarding symptoms, the frequency of hoarding, the degree of fear, and the negative emotions (depression, anxiety, stress) caused by COVID-19. Research data showed that fear of COVID-19 was significantly correlated with hoarding behavior (p < 0.05). Fear of COVID-19 was significantly lower in the student sample than in the nonstudent sample (p < 0.05). Negative emotions played a mediating role in the relationship between fear of COVID-19 and hoarding behavior (p < 0.05). Educational and economic levels moderated this process, but social status did not. Compared with the student sample, educational background and income had less of a moderating effect on the depression, anxiety, and stress caused by fear of COVID-19 in the nonstudent sample. However, these factors had a more regulative effect on the clutter and excessive acquisition behavior caused by depression, anxiety, and stress, although not on difficulty discarding. These findings suggest that reduce negative emotions in the population, improve cognitive levels, and provide financial support from governments may be effective ways to reduce hoarding symptoms.

Mobility support for disadvantaged and disabled travelers during pandemic or similar situations.

The COVID-19 lockdown has reduced public transportation service to the disadvantaged and disabled people who urgently need adequate mobility to obtain essential suppliers. This paper aims to improve the life quality of people with disabilities and elderly people by addressing social exclusion, accessibility, and mobility issues. Demand responsive transport services are frequently offered in the context of door-to-door transportation of the elderly and persons with disabilities. We study and compare two frameworks. We apply both Sample average approximation (SAA) and Rolling Horizon (RH) to optimize a car sharing system for the total cost, including initiation cost and operation cost after fleet size is determined. The model is implemented with given geographic conditions and other local information to be tailored for specific applications for local communities. Given that no historical data is available, random sample data is generated to simulate expected demands. We consider three types of probability distributions for daily demand data, and the results generated using three different distributions are being examined and compared. The research shows that the demand data following a normal distribution results in the minimum total cost. Additionally, we study the impact of several factors on total cost, including demand fulfillment rates and operation hours. Our results suggest that the impact of fulfillment rate on fleet size is exponential after a threshold under all three types of daily demand data, and extended operation hours can significantly reduce the total cost. Finally, the paper provides applicable frameworks for city planners, NPOs, and policymakers to better allocate limited resources to implement the carsharing system when little to no historical travel information is available for low-density population areas. It is anticipated that the outcome from this research would benefit disadvantaged and disabled travelers during COVID-19 or similar difficult situations in the future.

Impact of change in traffic flow on vehicle non-exhaust PM2.5 and PM10 emissions: A case study of the M25 motorway, UK.

This study quantifies the change in traffic flow on the M25 motorway in the UK due to the COVID-19 outbreak. Moreover, the impact of the change in traffic flow on non-exhaust PM2.5 and PM10 emissions for different categories of vehicle was explored. During the year of the COVID-19 outbreak (March 2020 to February 2021), the total traffic flows of passenger cars (PCs), light goods vehicles (LGVs), heavy goods vehicles (HGVs), and long HGVs on the M25 motorway decreased by 38.6%, 27.6%, 15.9% and 7.2%, respectively, in comparison to the previous year. Correspondingly, the total mass of non-exhaust emissions (PM2.5 and PM10) of PCs, LGVs, HGVs, and long HGVs reduced by 38.7%, 27.3%, 16.2% and 7%, respectively. The traffic flows per year before and during the COVID-19 outbreak of long HGVs were 87.2% and 80.7% less than those of PCs. Correspondingly, the long HGVs emitted 10.2% less but 36.3% more PM2.5 emissions, as well as 10.9% and 66.7% more PM10 emissions than the latter, indicating that long HGVs contribute much more to non-exhaust particles than PCs. In addition, it was found that resuspension of road dust on the M25 motorway was the largest contributor to air pollution among non-exhaust emissions, followed by road wear, tyre wear, and brake wear particles.

Disparities in Telehealth Utilization in a Population of Publicly Insured Children During the COVID-19 Pandemic.

Telehealth became a crucial vehicle for health care delivery in the United States during the COVID-19 pandemic. However, little research exists on inequities in telehealth utilization among the pediatric population. This study examines disparities in telehealth utilization in a population of publicly insured children. This observational, retrospective study used administrative data from Alabama's stand-alone Children's Health Insurance Program, ALL Kids. Rates of any telehealth use for March to December 2020 were examined. In addition-to capture lack of health care utilization-rates of having no medical claims were examined and compared with March to December 2019 and 2018. Multinomial logit models were estimated to investigate how telehealth use and having no medical claims (reference category: having medical claims but no telehealth) were associated with race/ethnicity, rural-urban residence, and family income. Of the 106,478 enrollees over March to December 2020, 13.4% had any telehealth use and 24.7% had no medical claims. The latter was greater than no medical claims in 2019 (19.5%) and 2018 (20.7%). Black and Hispanic children had lower odds of any telehealth use (odds ratio [OR]: 0.81, P < 0.01; OR: 0.68, P < 0.01) and higher odds of no medical claims (OR: 1.11, P < 0.05; OR: 1.73, P < 0.05) than non-Hispanic White children. Rural residents had lower odds of telehealth use than urban residents. Those in the highest family income-based fee group had higher odds of telehealth use than the lowest family income-based fee group. As telehealth will likely continue to play an important role in health care delivery, additional efforts/investments are required to ensure telehealth does not further exacerbate inequities in pediatric health care access.

Associations Between Online Learning, Smartphone Addiction Problems, and Psychological Symptoms in Chinese College Students After the COVID-19 Pandemic.

Background: Smartphone-based online education gained popularity during and after the COVID-19 pandemic. Although recent studies have highlighted the association between problematic smartphone use (PSU) and mental health symptoms, the potential role of online learning in this relationship remains unclear. This study aimed to analyze the relationships between higher education modes, PSU, and related psychological symptoms in university students. Methods: A total of 1,629 Chinese university students from five provinces completed a web-based questionnaire survey between March 2020 and October 2021. Demographic characteristics and learning conditions were recorded. All participants completed the Smartphone Addiction Scale-Short Version, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Athens Insomnia Scale. Multiple regressions models and stratified analyses were used to examine the association between online education mode, PSU, and symptoms of depression, anxiety, and insomnia. Results: The prevalence of PSU was 58.5%. Students who relied primarily on online learning had a higher prevalence of depressive symptoms (29.95% vs. 22.24%), anxiety symptoms (25.13% vs. 18.91%), and insomnia symptoms (75.89% vs. 70.27%) than those who relied on traditional face-to-face learning (Ps < 0.05). After adjusting for covariates, subjects with PSU were more likely to report depressive symptoms (AdjOR = 3.14, 95% CI = 2.26-4.37), anxiety symptoms (AdjOR = 3.73, 95% CI = 2.13-4.59), and insomnia symptoms (AdjOR = 2.96, 95% CI = 2.23-3.92) than those without PSU. Furthermore, the associations of PSU with depressive symptoms (OR = 4.66 vs. 2.33, P for interaction = 0.015) and anxiety symptoms (OR = 6.05 vs. 2.94, P for interaction = 0.021) were more pronounced in the online learning group. Conclusion: Our study provides preliminary evidence that Chinese university students have serious smartphone addiction problems, which are associated with depressive, anxiety, and insomnia symptoms. Online learning is found to exacerbate PSU and mental health problems. Our findings provide valuable information for targeted psychological interventions in the post-COVID-19 era.

mRNA based vaccines provide broad protection against different SARS-CoV-2 variants of concern.

In order to overcome the pandemic of COVID-19, messenger RNA (mRNA)-based vaccine has been extensively researched as a rapid and versatile strategy. Herein, we described the immunogenicity of mRNA-based vaccines for Beta and the most recent Omicron variants. The homologous mRNA-Beta and mRNA-Omicron and heterologous Ad5-nCoV plus mRNA vaccine exhibited high-level cross-reactive neutralization for Beta, original, Delta, and Omicron variants. It indicated that the COVID-19 mRNA vaccines have great potential in the clinical use against different SARS-CoV-2 variants.

SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID-19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID-19. Plasma VEGF level was particularly elevated in patients with GI symptoms and significantly correlated with intestinal edema and disease progression. Through an animal model mimicking intestinal inflammation upon stimulation with SARS-CoV-2 spike protein, we further revealed that VEGF was over-produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS-CoV-2 spike promoted VEGF production through activating the Ras-Raf-MEK-ERK signaling in enterocytes, but not in endothelium, and inducing permeability and inflammation. Blockage of the ERK/VEGF axis was able to rescue vascular permeability and alleviate intestinal inflammation in vivo. These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID-19.

SARS-CoV-2 membrane protein causes the mitochondrial apoptosis and pulmonary edema via targeting BOK.

Deaths caused by coronavirus disease 2019 (COVID-19) are largely due to the lungs edema resulting from the disruption of the lung alveolo-capillary barrier, induced by SARS-CoV-2-triggered pulmonary cell apoptosis. However, the molecular mechanism underlying the proapoptotic role of SARS-CoV-2 is still unclear. Here, we revealed that SARS-CoV-2 membrane (M) protein could induce lung epithelial cells mitochondrial apoptosis. Notably, M protein stabilized B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) via inhibiting its ubiquitination and promoted BOK mitochondria translocation. The endodomain of M protein was required for its interaction with BOK. Knockout of BOK by CRISPR/Cas9 increased cellular resistance to M protein-induced apoptosis. BOK was rescued in the BOK-knockout cells, which led to apoptosis induced by M protein. M protein induced BOK to trigger apoptosis in the absence of BAX and BAK. Furthermore, the BH2 domain of BOK was required for interaction with M protein and proapoptosis. In vivo M protein recombinant lentivirus infection induced caspase-associated apoptosis and increased alveolar-capillary permeability in the mouse lungs. BOK knockdown improved the lung edema due to lentivirus-M protein infection. Overall, M protein activated the BOK-dependent apoptotic pathway and thus exacerbated SARS-CoV-2 associated lung injury in vivo. These findings proposed a proapoptotic role for M protein in SARS-CoV-2 pathogenesis, which may provide potential targets for COVID-19 treatments.

Amantadine-assembled nanostimulator enhances dimeric RBD antigen-elicited cross-neutralization against SARS-CoV-2 strains.

There is an urgent need to develop new vaccination strategies to elevate the cross-neutralization against different SARS-CoV-2 strains. In this study, we construct the spherical amantadine-assembled nanostimulator (AAS). Amantadine as immunostimulating molecules are displayed on the outermost layer of AAS. Molecular mechanism analysis reveals that AAS can activate RIG-I-like receptor (RLR) signaling pathway to increase the expression of type I interferons in vivo. AAS-mediated activation of RLR signaling pathway further promotes the maturation and proliferation of dendritic cells (DCs) and T helper cells (Ths), finally activating B cells to produce potent antibody responses. In performance evaluation experiments, the mixture of AAS and dimeric RBD significantly enhances RBD-specific humoral responses (4-fold IgG, 3.5-fold IgG2a, 3.3-fold IgG2b, 3.8-fold IgG3 and 1.3-fold IgM), in comparison to aluminum adjuvant-assistant dimeric RBD. Importantly, AAS dramatically elevates dimeric RBD-elicited cross-neutralization against different SARS-CoV-2 strains such as Wuhan-Hu-1 (9-fold), B.1.1.7 (UK variant, 15-fold), B.1.351 (South African variant, 4-fold) and B.1.617.2 (India variant, 7-fold). Our study verifies the mechanism of AAS in activating RLR signaling pathway in host immune system and highlights the power of AAS in improving antigen-elicited cross-neutralization against different SARS-CoV-2 strains.

TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection.

Limited understanding of T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impeded vaccine development and drug discovery for coronavirus disease 2019 (COVID-19). We found that triggering receptor expressed on myeloid cells 2 (TREM-2) was induced in T cells in the blood and lungs of patients with COVID-19. After binding to SARS-CoV-2 membrane (M) protein through its immunoglobulin domain, TREM-2 then activated the CD3ζ/ZAP70 complex, leading to STAT1 phosphorylation and T-bet transcription. In vitro stimulation with M protein-reconstituted pseudovirus or recombinant M protein, and TREM-2 promoted the T helper cell 1 (TH1) cytokines interferon-γ and tumor necrosis factor. In vivo infection of CD4­TREM-2 conditional knockout mice with murine coronavirus mouse hepatitis virus A-59 showed that intrinsic TREM-2 in T cells enhanced TH1 response and viral clearance, thus aggravating lung destruction. These findings demonstrate a previously unidentified role for TREM-2 in SARS-CoV-2 infection, and suggest potential strategies for drug discovery and clinical management of COVID-19.

Multi-Scale Nanoarchitectured Fibrous Networks for High-Performance, Self-Sterilization, and Recyclable Face Masks.

Airborne particulate matter (PM) pollutants, especially with nanoscale size, have caused serious public health issues. The global demand for high-performance and recyclable face masks is increasing dramatically, especially during the COVID-19 pandemic. However, present masks suffer from low-efficiency interception of PM0.3 /pathogen, limited air permeability, and incapacity to reuse and recycle. Here, multi-scale nanoarchitectured nanofiber/carbon nanotube (NF/CNT) networks are constructed by a needleless-electrospinning/spraying-netting strategy, enabling well-dispersed CNT networks (diameter ≈ 25 nm) welded on charged nanofibrous scaffolds (diameter > 100 nm) layer by layer. The optimized NF/CNT networks possess a fluffy structure with narrow-distribution small pores (size ≈ 400 nm), "free molecular flow" behavior, and electrostatic adsorption property, thereby exhibiting high filtration efficiency (>99.994% PM0.3 removal) and low resistance (<0.05% atmosphere pressure). Furthermore, they demonstrate reliable and ultra-fast photothermal-driven self-sterilization (>99.986% in 5 min) under 1 sun and electrothermal-driven self-sterilization (>99.9999% in 2 min) in sunless scenes owing to their unique nanoarchitecture. Most importantly, the abandoned NF/CNT filters can be fully recycled as high-performance solar vapor generators to desalinate seawater (3.56 L m-2 d-1 ). This work offers a fascinating solution to reduce disease transmission, resource consumption, and environmental burdens.

Urban greenery cushions the decrease in leisure-time physical activity during the COVID-19 pandemic: A natural experimental study.

The coronavirus disease 2019 (COVID-19) pandemic and related social distancing measures have altered the daily lifestyles of people worldwide. Although studies on this disease are emerging rapidly, less is known about the impacts of COVID-19 and urban greenery on leisure-time physical activity, which is critical to maintain health for urban residents during the pandemic. In this study, we used a natural experimental research design to identify whether urban greenery cushions the decrease in leisure-time physical activity caused by the pandemic and related social distancing measures in a high-density city. The two-wave physical activity data (before and during the pandemic) were collected for urban residents in neighborhoods with high or low levels of greenery. The results of difference-in-differences model suggest that urban greenery mitigated the decrease in physical activity during the pandemic. People who lived in greener neighborhoods experienced a lesser decrease in the leisure-time physical activity level than those who lived in less green neighborhoods. Additionally, people who lived in greener neighborhoods experienced increased levels of physical activity related to visits to country parks during the pandemic. These findings suggest that urban green spaces play a significant role in shaping physical activity and providing a refuge for the public during crises. Our study is among the first to investigate the impact of urban greenery on pandemic-induced changes in leisure-time physical activity in densely populated Asian cities, and our findings shed light on the potential protective role of urban greenery on public health during the COVID-19 pandemic and beyond.