Environment and natural resources degradation under COVID-19 crises: Recovery post pandemic.

Environmental stability improved during the covid 19 pandemic when production and industrial activities, and natural resources depletion processes stopped during the lockdown environment worldwide; however, based on the judgment of COP26 and the recent COP27, environmental degradation increased in the world in post-pandemic; therefore, policymakers and researchers re-focused their attention on the determinants of CO2 in economies. Hence, this study investigates the nexus of natural resource rents, including oil rents, mineral rents, and coal rents, on the carbon emissions of upper-middle-income economies from 1984 to 2021. The study included economic growth and renewable energy as additional determinants. We have presented detailed time series methods that aid in examining the modeled variables characteristics in the current research, i.e., ADF and ADF-GLS for a unit root in the data variables and considering their stationarity, Johansen cointegration for long-term cointegration among variables, FMOLS, DOLS and CCR for the long run elasticities between dependent and independent variables and Granger causality test in our range of methods. Robustness checks analysis is done through a non-parametric approach by quantile regression and robust regression analysis. Our results exhibit that two natural resource rents that are oil rents and coal rents, have adverse impacts on carbon emissions, and both are positive and significant. In contrast, mineral rents have no statistical significance and role in the carbon emissions of upper-middle-income economies. Moreover, economic growth and renewable energy also positively and significantly impact carbon emissions. Granger causality analysis exerts that natural resources rents, except for mineral rents, economic growth, and renewable energy, all granger causes CO2 emissions, and the feedback is also true. The relevant findings are suitable for policymakers in upper-middle-income economies to ensure environmental sustainability in upper-middle-income economies.

Microneedle-based interstitial fluid extraction for drug analysis: Advances, challenges, and prospects.

Similar to blood, interstitial fluid (ISF) contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis. However, current ISF extraction techniques require bulky instruments and are both time-consuming and complicated, which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles. Currently, microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis. The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring, while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification. Herein, we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

Metavirome Analysis Reveals a High Prevalence of Porcine Hemagglutination Encephalomyelitis Virus in Clinically Healthy Pigs in China.

Six swine coronaviruses (SCoVs), which include porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine hemagglutination encephalomyelitis virus (PHEV), porcine respiratory coronavirus (PRCV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV), have been reported as infecting and causing serious diseases in pigs. To investigate the genetic diversity and spatial distribution of SCoVs in clinically healthy pigs in China, we collected 6400 nasal swabs and 1245 serum samples from clinically healthy pigs at slaughterhouses in 13 provinces in 2017 and pooled them into 17 libraries by type and region for next-generation sequencing (NGS) and metavirome analyses. In total, we identified five species of SCoVs, including PEDV, PDCoV, PHEV, PRCV, and TGEV. Strikingly, PHEV was detected from all the samples in high abundance and its genome sequences accounted for 75.28% of all coronaviruses, while those belonging to TGEV (including PRCV), PEDV, and PDCoV were 20.4%, 2.66%, and 2.37%, respectively. The phylogenetic analysis showed that two lineages of PHEV have been circulating in pig populations in China. We also recognized two PRCVs which lack 672 nucleotides at the N-terminus of the S gene compared with that of TGEV. Together, we disclose preliminarily the genetic diversities of SCoVs in clinically healthy pigs in China and provide new insights into two SCoVs, PHEV and PRCV, that have been somewhat overlooked in previous studies in China.

Underlying medical conditions and anti-SARS-CoV-2 spike IgG antibody titers after two doses of BNT162b2 vaccination: A cross-sectional study.

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30-50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76-0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42-0.95) and 0.77 (0.63-0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes.

Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases.

Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease.

Microporous Matrimid/PIM-1 Thin Film Composite Membranes with Narrow Pore Size Distribution used for Molecular Separation in Organic Solvents.

Polymers of intrinsic microporosity (PIMs) are a class of microporous organic materials that contain interconnected pores of less than 2 nm in diameter. Such materials are of great potential used in membranes for molecular separation, such as drug fractionation in pharmaceutical industry. However, the PIMs membranes are often susceptible to low separation selectivity toward different molecules due to their wide pore size distribution. Herein, a linear polyimide, Matrimid, is incorporated with PIM-1 (a typical member of PIMs) by solution blending, and the blends are dip-coated onto a polyimide P84 support membrane to prepare thin-film composite (TFC) membranes to control pore size distribution while keep high microporosity. The component miscibility, pore characteristics, and molecular separation performances of the Matrimid/PIM-1 TFC membranes are investigated in detail. The Matrimid and PIM-1 are partially miscible due to their similar Hansen solubility parameters. The Matrimid endows the selective layers (coatings) with narrower pore size distribution due to more compact chain packing. The prepared Matrimid/PIM-1 TFC membranes show high selectivity for separation of riboflavin (80% of retention) and isatin (only 5% of retention). The developed membranes exhibit great potential for separating molecules with different molecular weights.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.

Intranasal delivery of replicating mRNA encoding hACE2-targeting antibody against SARS-CoV-2 Omicron infection in the hamster.

The Omicron variant is sweeping the world, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein, making broad-spectrum SARS-CoV-2 prevention or therapeutical strategies urgently needed. Previously, we have reported a hACE2-targeting neutralizing antibody 3E8, which could efficiently block both prototype SARS-CoV-2 and Delta variant infections in prophylactic mouse models, having the potential of broad-spectrum to prevent SARS-CoV-2. However, preparation of monoclonal neutralizing antibodies is severely limited by the time-consuming process and the relative high cost. Here, we utilized a modified VEEV replicon with two subgenomic (sg) promoters engineered to express the light and heavy chains of the 3E8 mAb. The feasibility and protective efficacy of replicating mRNA encoding 3E8 against Omicron infection in the hamster were demonstrated through the lung targeting delivery with the help of VEEV-VRP. Overall, we developed a safe and cost-effective platform of broad-spectrum to prevent SARS-CoV-2 infection.

Clinical application of prion-like seeding in α-synucleinopathies: Early and non-invasive diagnosis and therapeutic development.

The accumulation and deposition of misfolded α-synuclein (α-Syn) aggregates in the brain is the central event in the pathogenesis of α-synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. Currently, the diagnosis of these diseases mainly relies on the recognition of advanced clinical manifestations. Differential diagnosis among the various α-synucleinopathies subtypes remains challenging. Misfolded α-Syn can template its native counterpart into the same misfolded one within or between cells, behaving as a prion-like seeding. Protein-misfolding cyclic amplification and real-time quaking-induced conversion are ultrasensitive protein amplification assays initially used for the detection of prion diseases. Both assays showed high sensitivity and specificity in detection of α-synucleinopathies even in the pre-clinical stage recently. Herein, we collectively reviewed the prion-like properties of α-Syn and critically assessed the detection techniques of α-Syn-seeding activity. The progress of test tissues, which tend to be less invasive, is presented, particularly nasal swab, which is now widely known owing to the global fight against coronavirus disease 2019. We highlight the clinical application of α-Syn seeding in early and non-invasive diagnosis. Moreover, some promising therapeutic perspectives and clinical trials targeting α-Syn-seeding mechanisms are presented.

The Effect of Organizational Trust on Turnover Intention of Rural Kindergarten Teachers: The Mediating Role of Teaching Efficacy and Job Satisfaction.

Recent studies have focused on turnover among rural kindergarten teachers. However, none of these studies have shown a clear connection between turnover intention and organizational trust, although there are studies in other areas showing that organizational trust can affect turnover intention. Drawing on a sample of 330 kindergarten teachers in rural areas, this study explores the mechanism of influence between organizational trust and turnover intention with teaching efficacy and job satisfaction as mediators. We found that organizational trust negatively impacted teachers' turnover intention, and this relationship was mediated by a significant chain mediating effect of teaching efficacy and job satisfaction. The findings enrich knowledge about turnover among rural kindergarten teachers and inspire us to create a more supportive organizational environment against the backdrop of the COVID-19 pandemic to improve job satisfaction and alleviate turnover among rural kindergarten teachers.

Evaluation of Air Pollutants in Extra-Long Road Tunnel with the Combination of Pollutants Nonlinear Evolution and Machine Learning Method

The extra-long expressway tunnel has a high socio-economic effect on inter-regional development, with high traffic and strong traffic winds. Nevertheless, the impacts of the tunnel traffic volume on pollutant evolution are rarely considered. This study conducted a field measurement in a real-world extra-long highway tunnel for 578 days. For the first time, the nonlinear dynamics of traffic pollutants (CO, VOCs, NO2, PM2.5, PM10) were analyzed using the Multifractal Detrended Fluctuation Analysis approach. Using the Random Forest model, the impacts of traffic and environmental parameters on air quality were quantified. The findings indicated that COVID-19 had a considerable impact on tunnel traffic, although the variance in pollutant concentration was not very noteworthy. The bidirectional effect of traffic was the main reason for this phenomenon. The Canonical Correlation Analysis was unable to quantify the correlation between pollutants and environmental parameters. The pollutant concentration evolution has a steady power-law distribution structure. Further, an inverse Random Forest model was proposed to predict air pollutants. Compared with other prediction models (baseline and machine learning), the proposed model provided higher goodness of fit and lower prediction error, and the prediction accuracy was higher under the semi-enclosed structure of the tunnel. The relative deviations between the predictions and measured data are less than 5%. These findings ascertain the nonlinear evolutionary mechanisms of pollutants inside the expressway tunnel, thus eventually improving tunnel environmental sustainability. The data in this paper can be used to clarify the changes in the traffic environment under the COVID-19 lockdown.

SARS-CoV-2 and Emerging Variants: Unmasking Structure, Function, Infection, and Immune Escape Mechanisms.

As of April 1, 2022, over 468 million COVID-19 cases and over 6 million deaths have been confirmed globally. Unlike the common coronavirus, SARS-CoV-2 has highly contagious and attracted a high level of concern worldwide. Through the analysis of SARS-CoV-2 structural, non-structural, and accessory proteins, we can gain a deeper understanding of structure-function relationships, viral infection mechanisms, and viable strategies for antiviral therapy. Angiotensin-converting enzyme 2 (ACE2) is the first widely acknowledged SARS-CoV-2 receptor, but researches have shown that there are additional co-receptors that can facilitate the entry of SARS-CoV-2 to infect humans. We have performed an in-depth review of published papers, searching for co-receptors or other auxiliary membrane proteins that enhance viral infection, and analyzing pertinent pathogenic mechanisms. The genome, and especially the spike gene, undergoes mutations at an abnormally high frequency during virus replication and/or when it is transmitted from one individual to another. We summarized the main mutant strains currently circulating global, and elaborated the structural feature for increased infectivity and immune evasion of variants. Meanwhile, the principal purpose of the review is to update information on the COVID-19 outbreak. Many countries have novel findings on the early stage of the epidemic, and accruing evidence has rewritten the timeline of the outbreak, triggering new thinking about the origin and spread of COVID-19. It is anticipated that this can provide further insights for future research and global epidemic prevention and control.

Hydroxamate and thiosemicarbazone: Two highly promising scaffolds for the development of SARS-CoV-2 antivirals.

The emerging COVID-19 pandemic generated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has severely threatened human health. The main protease (Mpro) of SARS-CoV-2 is promising target for antiviral drugs, which plays a vital role for viral duplication. Development of the inhibitor against Mpro is an ideal strategy to combat COVID-19. In this work, twenty-three hydroxamates 1a-i and thiosemicarbazones 2a-n were identified by FRET screening to be the potent inhibitors of Mpro, which exhibited more than 94% (except 1c) and more than 69% inhibition, and an IC50 value in the range of 0.12-31.51 and 2.43-34.22 µM, respectively. 1a and 2b were found to be the most effective inhibitors in the hydroxamates and thiosemicarbazones, with an IC50 of 0.12 and 2.43 µM, respectively. Enzyme kinetics, jump dilution and thermal shift assays revealed that 2b is a competitive inhibitor of Mpro, while 1a is a time-dependently inhibitor; 2b reversibly but 1a irreversibly bound to the target; the binding of 2b increased but 1a decreased stability of the target, and DTT assays indicate that 1a is the promiscuous cysteine protease inhibitor. Cytotoxicity assays showed that 1a has low, but 2b has certain cytotoxicity on the mouse fibroblast cells (L929). Docking studies revealed that the benzyloxycarbonyl carbon of 1a formed thioester with Cys145, while the phenolic hydroxyl oxygen of 2b formed H-bonds with Cys145 and Asn142. This work provided two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.

Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.

The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model in vivo. The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. In vitro mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. IMPORTANCE COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.

Risk assessment of airborne transmission of COVID-19 by asymptomatic individuals under different practical settings

The lack of quantitative risk assessment of airborne transmission of COVID-19 under practical settings leads to large uncertainties and inconsistencies in our preventive measures. Combining in situ measurements and numerical simulations, we quantify the exhaled aerosols from normal respiratory behaviors and their transport under elevator, small classroom and supermarket settings to evaluate the risk of inhaling potentially virus-containing aerosols. Our results show that the design of ventilation is critical for reducing the risk of aerosol encounters. Inappropriate design can significantly limit the efficiency of aerosol removal, create local hot spots with orders of magnitude higher risks, and enhance aerosol deposition causing surface contamination. Additionally, our measurements reveal the presence of substantial fraction of crystalline aerosols from normal breathing and its strong correlation with breathing depth.

SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate.

Thrombotic complication has been an important symptom in critically ill patients with COVID-19. It has not been clear whether the virus spike (S) protein can directly induce blood coagulation in addition to inflammation. Heparan sulfate (HS)/heparin, a key factor in coagulation process, was found to bind SARS-CoV-2 S protein with high affinity. Herein, we found that the S protein can competitively inhibit the bindings of antithrombin and heparin cofactor II to heparin/HS, causing abnormal increase in thrombin activity. SARS-CoV-2 S protein at a similar concentration (~10 µg/mL) as the viral load in critically ill patients can cause directly blood coagulation and thrombosis in zebrafish model. Furthermore, exogenous heparin/HS can significantly reduce coagulation caused by S protein, pointing to a potential new direction to elucidate the etiology of the virus and provide fundamental support for anticoagulant therapy especially for the COVID-19 critically ill patients.