Unbalanced emission reductions of different species and sectors in China during COVID-19 lockdown derived by multi-species surface observation assimilation

The unprecedented lockdown of human activities during the COVID-19 pandemic has significantly influenced social life in China. However, understanding the impact of this unique event on the emissions of different species is still insufficient, prohibiting the proper assessment of the environmental impacts of COVID-19 restrictions. Here we developed a multi-air-pollutant inversion system to simultaneously estimate the emissions of NOx, SO2, CO, PM2.5 and PM10 in China during COVID-19 restrictions with high temporal (daily) and horizontal (15 km) resolutions. Subsequently, contributions of emission changes versus meteorological variations during the COVID-19 lockdown were separated and quantified. The results demonstrated that the inversion system effectively reproduced the actual emission variations in multi-air pollutants in China during different periods of COVID-19 lockdown, which indicate that the lockdown is largely a nationwide road traffic control measure with NOx emissions decreasing substantially by ∼40 %. However, emissions of other air pollutants were found to only decrease by∼10% because power generation and heavy industrial processes were not halted during lockdown, and residential activities may actually have increased due to the stay-at-home orders. Consequently, although obvious reductions of PM2.5 concentrations occurred over the North China Plain (NCP) during the lockdown period, the emission change only accounted for 8.6 % of PM2.5 reductions and even led to substantial increases in O3. The meteorological variation instead dominated the changes in PM2.5 concentrations over the NCP, which contributed 90 % of the PM2.5 reductions over most parts of the NCP region. Meanwhile, our results suggest that the local stagnant meteorological conditions, together with inefficient reductions of PM2.5 emissions, were the main drivers of the unexpected PM2.5 pollution in Beijing during the lockdown period. These results highlighted that traffic control as a separate pollution control measure has limited effects on the coordinated control of O3 and PM2.5 concentrations under current complex air pollution conditions in China. More comprehensive and balanced regulations for multiple precursors from different sectors are required to address O3 and PM2.5 pollution in China.

A case of complete recovery in a hypereosinophilic dermatitis patient with dupilumab.

BACKGROUND: Hypereosinophilic dermatitis (HED) is a subtype of hypereosinophilic syndrome (HES). Glucocorticoids are preferred for treatment but carry substantial side effect profiles. Symptoms of HED may recur after systemic glucocorticoid tapering. As an interleukin-4 receptor (IL-4Rα) monoclonal antibody targeting interleukin-4 (IL-4) and interleukin-13 (IL-13), dupilumab might be an efficacious adjuvant therapy for HED. METHOD: We report a young male diagnosed with HED who suffered from erythematous papules with pruritus for over five years. Once reducing the dosage of glucocorticoid was, his skin lesions relapsed. RESULTS: After using dupilumab, the patient's condition significantly improved with the glucocorticoid dosing decreased successfully. CONCLUSION: In conclusion, we report a new application of dupilumab in HED patients, especially with difficulties in reducing the glucocorticoid dose.

Spatiotemporal Evolution of Carbon Emissions According to Major Function-Oriented Zones: A Case Study of Guangdong Province, China.

Studying the spatiotemporal evolution of carbon emissions from the perspective of major function-oriented zones (MFOZs) is crucial for making a carbon reduction policy. However, most previous research has ignored the spatial characteristics and MFOZ influence. Using statistical and spatial analysis tools, we explored the spatiotemporal characteristics of carbon emissions in Guangdong Province from 2001 to 2021. The following results were obtained: (1) Carbon emissions fluctuated from 2020 to 2021 because of COVID-19. (2) Over the last 20 years, the proportion of carbon emissions from urbanization development zones (UDZs) has gradually decreased, whereas those of the main agricultural production zones (MAPZs) and key ecological function zones (KEFZs) have increased. (3) Carbon emissions efficiency differed significantly among the three MFOZs. (4) Carbon emissions from coastal UDZs were increasingly apparent; however, the directional characteristics of MAPZ and KEFZ emissions were not remarkable. (5) Carbon transfer existed among the three kinds of MFOZs, resulting in the economy and carbon emissions being considerably misaligned across Guangdong Province. These results indicated that the MFOZ is noteworthy in revealing how carbon emissions evolved. Furthermore, spatiotemporal characteristics, especially spatial characteristics, can help formulate carbon reduction policies for realizing carbon peak and neutrality goals in Guangdong Province.

Microfluidic space coding for multiplexed nucleic acid detection via CRISPR-Cas12a and recombinase polymerase amplification.

Fast, inexpensive, and multiplexed detection of multiple nucleic acids is of great importance to human health, yet it still represents a significant challenge. Herein, we propose a nucleic acid testing platform, named MiCaR, which couples a microfluidic device with CRISPR-Cas12a and multiplex recombinase polymerase amplification. With only one fluorescence probe, MiCaR can simultaneously test up to 30 nucleic acid targets through microfluidic space coding. The detection limit achieves 0.26 attomole, and the multiplexed assay takes only 40 min. We demonstrate the utility of MiCaR by efficiently detecting the nine HPV subtypes targeted by the 9-valent HPV vaccine, showing a sensitivity of 97.8% and specificity of 98.1% in the testing of 100 patient samples at risk for HPV infection. Additionally, we also show the generalizability of our approach by successfully testing eight of the most clinically relevant respiratory viruses. We anticipate this effective, undecorated and versatile platform to be widely used in multiplexed nucleic acid detection.

Changes in primary and secondary aerosols during a controlled Chinese New Year.

Large reductions in anthropogenic emissions during the Chinese New Year (CNY) holiday in Beijing have been well reported. However, the changes during the CNY of 2021 are different because most people stayed in Beijing to control the spread of coronavirus disease (COVID-19). Here a high-resolution aerosol mass spectrometer (HR-AMS) was deployed for characterization of the changes in size-resolved aerosol composition and sources during the CNY. We found that the reductions in traffic-related NOx and fossil fuel-related organic aerosol (OA), and cooking OA (1.3-12.7%) during the CNY of 2021 were much smaller than those in previous CNY holidays of 2013, 2015, and 2020. In contrast, the mass concentrations of secondary aerosol species except nitrate showed ubiquitous increases (17.6-30.4%) during the CNY of 2021 mainly due to a 4-day severe haze episode. OA composition also changed substantially during the CNY of 2021. In particular, we observed a large increase by nearly a factor of 2 in oxidized primary OA likely from biomass burning, and a decrease of 50.1% in aqueous-phase secondary OA. A further analysis of the severe haze episode during the CNY illustrated a rapid transition of secondary formation from photochemical to aqueous-phase processing followed by a scavenging process, leading to significant changes in aerosol composition, size distributions, and oxidation degree of OA. A parameterization relationship between oxygen-to-carbon (O/C) and f44 (fraction of m/z 44 in OA) from a collocated capture vaporizer aerosol chemical speciation monitor (CV-ACSM) was developed, which has a significant implication for characterization of OA evolution and the impacts on hygroscopicity due to the rapidly increased deployments of CV-ACSM worldwide.

Telomere G-triplex lights up Thioflavin T for RNA detection: new wine in an old bottle.

Few reports are found working on the features and functions of the human telomere G-triplex (ht-G3) though the telomere G-quadruplex has been intensely studied and widely implemented to develop various biosensors. We herein report that ht-G3 lights up Thioflavin T (ThT) and establish a sensitive biosensing platform for RNA detection by introducing a target recycling strategy. An optimal condition was selected out for ht-G3 to promote ThT to generate a strong fluorescence. Accordingly, an ht-G3-based molecular beacon was successfully designed against the corresponding RNA sequence of the SARS-CoV-2 N-gene. The sensitivity for the non-amplified RNA target achieves 0.01 nM, improved 100 times over the conventional ThT-based method. We believe this ht-G3/ThT-based label-free strategy could be widely applied for RNA detection.

Various surgical interventions in cases of complicated hepatic echinococcosis with intracystic bile leakage

Objective: To explore an effective surgical intervention strategy for hepatic echinococcosis complicated with intracystic bile leakage.

The effect of self-limiting on the prevention and control of the diffuse COVID-19 epidemic with delayed and temporal-spatial heterogeneous.

BACKGROUND: The global spread of the novel coronavirus pneumonia is still continuing, and a new round of more serious outbreaks has even begun in some countries. In this context, this paper studies the dynamics of a type of delayed reaction-diffusion novel coronavirus pneumonia model with relapse and self-limiting treatment in a temporal-spatial heterogeneous environment. METHODS: First, focus on the self-limiting characteristics of COVID-19, incorporate the relapse and self-limiting treatment factors into the diffusion model, and study the influence of self-limiting treatment on the diffusion of the epidemic. Second, because the traditional Lyapunov stability method is difficult to determine the spread of the epidemic with relapse and self-limiting treatment, we introduce a completely different method, relying on the existence conditions of the exponential attractor of our newly established in the infinite-dimensional dynamic system to determine the diffusion of novel coronavirus pneumonia. Third, relapse and self-limiting treatment have led to a change in the structure of the delayed diffusion COVID-19 model, and the traditional basic reproduction number [Formula: see text] no longer has threshold characteristics. With the help of the Krein-Rutman theorem and the eigenvalue method, we studied the threshold characteristics of the principal eigenvalue and found that it can be used as a new threshold to describe the diffusion of the epidemic. RESULTS: Our results prove that the principal eigenvalue [Formula: see text] of the delayed reaction-diffusion COVID-19 system with relapse and self-limiting treatment can replace the basic reproduction number [Formula: see text] to describe the threshold effect of disease transmission. Combine with the latest official data and the prevention and control strategies, some numerical simulations on the stability and global exponential attractiveness of the diffusion of the COVID-19 epidemic in China and the USA are given. CONCLUSIONS: Through the comparison of numerical simulations, we find that self-limiting treatment can significantly promote the prevention and control of the epidemic. And if the free activities of asymptomatic infected persons are not restricted, it will seriously hinder the progress of epidemic prevention and control.

Advances in mRNA and other vaccines against MERS-CoV.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus (CoV). Belonging to the same beta-CoV genus as severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and SARS-CoV-2, MERS-CoV has a significantly higher fatality rate with limited human-to-human transmissibility. MERS-CoV causes sporadic outbreaks, but no vaccines have yet been approved for use in humans, thus calling for continued efforts to develop effective vaccines against this important CoV. Similar to SARS-CoV-1 and SARS-CoV-2, MERS-CoV contains 4 structural proteins, among which the surface spike (S) protein has been used as a core component in the majority of currently developed MERS-CoV vaccines. Here, we illustrate the importance of the MERS-CoV S protein as a key vaccine target and provide an update on the currently developed MERS-CoV vaccines, including those based on DNAs, proteins, virus-like particles or nanoparticles, and viral vectors. Additionally, we describe approaches for designing MERS-CoV mRNA vaccines and explore the role and importance of naturally occurring pseudo-nucleosides in the design of effective MERS-CoV mRNA vaccines. This review also provides useful insights into designing and evaluating mRNA vaccines against other viral pathogens.

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2pos subjects.

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.

Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants.

Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with comparable potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in the mouse model. Compared with the soluble spike, the I3-01v9 SApNP showed sixfold longer retention, fourfold greater presentation on follicular dendritic cell dendrites, and fivefold stronger germinal center reactions in lymph node follicles.

G-triplex: A new type of CRISPR-Cas12a reporter enabling highly sensitive nucleic acid detection.

CRISPR-Cas12a (Cpf1) trans-cleaves ssDNA and this feature has been widely harnessed for nucleic acid detection. Herein, we introduce a new type of Cas12a reporter, G-triplex (G3), and a highly sensitive biosensor termed G-CRISPR. We proved that Cas12a trans-cleaves G3 structures in about 10 min and G3 can serve as an excellent reporter based on the cleavage-induced high-order structure disruption. G3 reporter improves the analytical sensitivity up to 20 folds, enabling the detection of unamplified and amplified DNA as low as 50 pmol and 0.1 amol (one copy/reaction), respectively. G-CRISPR has been utilized for the analysis of 27 PCR-amplified patient samples with HPV infection risk based on both fluorescence and lateral flow assays, resulting in 100% concordance between the two. In comparison with the clinical results, it achieved overall specificity and sensitivity of 100% and 94.7%, respectively. These results suggest that G-CRISPR can serve as a rapid, sensitive, and reliable biosensor, and could further expand the CRISPR toolbox in biomedical diagnostics.

Numerical study of COVID-19 spatial-temporal spreading in London.

A recent study reported that an aerosolized virus (COVID-19) can survive in the air for a few hours. It is highly possible that people get infected with the disease by breathing and contact with items contaminated by the aerosolized virus. However, the aerosolized virus transmission and trajectories in various meteorological environments remain unclear. This paper has investigated the movement of aerosolized viruses from a high concentration source across a dense urban area. The case study looks at the highly air polluted areas of London: University College Hospital (UCH) and King's Cross and St Pancras International Station (KCSPI). We explored the spread and decay of COVID-19 released from the hospital and railway stations with the prescribed meteorological conditions. The study has three key findings: the primary result is that the concentration of viruses decreases rapidly by a factor of 2-3 near the sources although the virus may travel from meters up to hundreds of meters from the source location for certain meteorological conditions. The secondary finding shows viruses released into the atmosphere from entry and exit points at KCSPI remain trapped within a small radial distance of < 50 m. This strengthens the case for the use of face coverings to reduce the infection rate. The final finding shows that there are different levels of risk at various door locations for UCH; depending on which door is used there can be a higher concentration of COVID-19. Although our results are based on London, since the fundamental knowledge processes are the same, our study can be further extended to other locations (especially the highly air polluted areas) in the world.

Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.

Vaccination against SARS-CoV-2 provides an effective tool to combat the COVID-19 pandemic. Here, we combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2. We first displayed the receptor-binding domain (RBD) on three self-assembling protein nanoparticle (SApNP) platforms using the SpyTag/SpyCatcher system. We then identified heptad repeat 2 (HR2) in S2 as the cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2GΔHR2), and displayed S2GΔHR2 on SApNPs. An antibody column specific for the RBD enabled tag-free vaccine purification. In mice, the 24-meric RBD-ferritin SApNP elicited a more potent neutralizing antibody (NAb) response than the RBD alone and the spike with two stabilizing proline mutations in S2 (S2P). S2GΔHR2 elicited twofold higher NAb titers than S2P, while S2GΔHR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2GΔHR2-presenting I3-01v9 SApNP also induced critically needed T cell immunity, thereby providing a promising vaccine candidate.

Predicting severe or critical symptoms in hospitalized patients with COVID-19 from Yichang, China.

OBJECTIVES: We aimed to identify potential risk factors for severe or critical coronavirus disease 2019 (COVID-19) and establish a prediction model based on significant factors. METHODS: A total of 370 patients with COVID-19 were consecutively enrolled at The Third People's Hospital of Yichang from January to March 2020. COVID-19 was diagnosed according to the COVID-19 diagnosis and treatment plan released by the National Health and Health Committee of China. Effect-size estimates are summarized as odds ratio (OR) and 95% confidence interval (CI). RESULTS: 326 patients were diagnosed with mild or ordinary COVID-19, and 44 with severe or critical COVID-19. After propensity score matching and statistical adjustment, eight factors were significantly associated with severe or critical COVID-19 (p <0.05) relative to mild or ordinary COVID-19. Due to strong pairwise correlations, only five factors, including diagnostic delay (OR, 95% CI, p: 1.08, 1.02 to 1.17, 0.048), albumin (0.82, 0.75 to 0.91, <0.001), lactate dehydrogenase (1.56, 1.14 to 2.13, 0.011), white blood cell (1.27, 1.08 to 1.50, 0.004), and neutrophil (1.40, 1.16 to 1.70, <0.001), were retained for model construction and performance assessment. The nomogram model based on the five factors had good prediction capability and accuracy (C-index: 90.6%). CONCLUSIONS: Our findings provide evidence for the significant contribution of five independent factors to the risk of severe or critical COVID-19, and their prediction was reinforced in a nomogram model.

Dynamic analysis of a delayed COVID-19 epidemic with home quarantine in temporal-spatial heterogeneous via global exponential attractor method.

As the COVID-19 epidemic has entered the normalization stage, the task of prevention and control remains very arduous. This paper constructs a time delay reaction-diffusion model that is closer to the actual spread of the COVID-19 epidemic, including relapse, time delay, home quarantine and temporal-spatial heterogeneous environment that affect the spread of COVID-19. These factors increase the number of equations and the coupling between equations in the system, making it difficult to apply the methods commonly used to discuss global dynamics, such as the Lyapunov function method. Therefore, we use the global exponential attractor theory in the infinite-dimensional dynamic system to study the spreading trend of the COVID-9 epidemic with relapse, time delay, home quarantine in a temporal-spatial heterogeneous environment. Using our latest results of global exponential attractor theory, the global asymptotic stability and the persistence of the COVID-19 epidemic are discussed. We find that due to the influence of relapse in the in temporal-spatial heterogeneity environment, the principal eigenvalue λ * can describe the spread of the epidemic more accurately than the usual basic reproduction number R 0 . That is, the non-constant disease-free equilibrium is globally asymptotically stable when λ * < 0 and the COVID-19 epidemic is persisting uniformly when λ * > 0 . Combine with the latest official data of the COVID-19 and the prevention and control strategies of different countries, some numerical simulations on the stability and global exponential attractiveness of the spread of the COVID-19 epidemic in China and the USA are given. The simulation results fully reflect the impact of the temporal-spatial heterogeneous environment, relapse, time delay and home quarantine strategies on the spread of the epidemic, revealing the significant differences in epidemic prevention strategies and control effects between the East and the West. The results of this study provide a theoretical basis for the current epidemic prevention and control.

Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.

Vaccination against SARS-CoV-2 provides an effective tool to combat the COIVD-19 pandemic. Here, we combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2. We first displayed the receptor-binding domain (RBD) on three self-assembling protein nanoparticle (SApNP) platforms using the SpyTag/SpyCatcher system. We then identified heptad repeat 2 (HR2) in S2 as the cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2GΔHR2), and displayed S2GΔHR2 on SApNPs. An antibody column specific for the RBD enabled tag-free vaccine purification. In mice, the 24-meric RBD-ferritin SApNP elicited a more potent neutralizing antibody (NAb) response than the RBD alone and the spike with two stabilizing proline mutations in S2 (S2P). S2GΔHR2 elicited two-fold-higher NAb titers than S2P, while S2GΔHR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2GΔHR2-presenting I3-01v9 SApNP also induced critically needed T-cell immunity, thereby providing a promising vaccine candidate.

Spread trend of COVID-19 epidemic outbreak in China: using exponential attractor method in a spatial heterogeneous SEIQR model.

In this paper we introduce a method of global exponential attractor in the reaction-diffusion epidemic model in spatial heterogeneous environment to study the spread trend and long-term dynamic behavior of the COVID-19 epidemic. First, we prove the existence of the global exponential attractor of general dissipative evolution systems. Then, by using the existence theorem, the global asymptotic stability and the persistence of epidemic are discussed. Finally, combine with the official data of the COVID-19 and the national control strategy, some numerical simulations on the stability and global exponential attractiveness of the COVID-19 epidemic are given. Simulations show that the spread trend of the epidemic is in line with our theoretical results, and the preventive measures taken by the Chinese government are effective.

A Familial Cluster of Infection Associated With the 2019 Novel Coronavirus Indicating Possible Person-to-Person Transmission During the Incubation Period.

An ongoing outbreak of pneumonia associated with 2019 novel coronavirus was reported in China. It is unclear whether the virus is infective exists during the incubation period, although person-to-person transmission has been reported elsewhere. We report the epidemiological features of a familial cluster of 4 patients in Shanghai, including an 88-year-old man with limited mobility who was exposed only to asymptomatic family members whose symptoms developed later. The epidemiological evidence has shown possible transmission of 2019 novel coronavirus during the incubation period.