Specific physiological responses to alkaline carbonate stress in rice (Oryza sativa) seedlings: organic acid metabolism and hormone signalling.

In recent years, alkaline soda soil has stimulated numerous biological research on plants under carbonate stress. Here, we explored the difference in physiological regulation of rice seedlings between saline (NaCl) and alkaline carbonate (NaHCO3 and Na2 CO3 ) stress. The rice seedlings were treated with 40mM NaCl, 40mM NaHCO3 and 20mM Na2 CO3 for 2h, 12h, 24h and 36h, their physiological characteristics were determined, and organic acid biosynthesis and metabolism and hormone signalling were identified by transcriptome analysis. The results showed that alkaline stress caused greater damage to their photosynthetic and antioxidant systems and led to greater accumulation of organic acid, membrane damage, proline and soluble sugar but a decreased jasmonic acid content compared with NaCl stress. Jasmonate ZIM-Domain (JAZ), the probable indole-3-acetic acid-amido synthetase GH3s, and the protein phosphatase type 2Cs that related to the hormone signalling pathway especially changed under Na2 CO3 stress. Further, the organic acid biosynthesis and metabolism process in rice seedlings were modified by both Na2 CO3 and NaHCO3 stresses through the glycolate/glyoxylate and pyruvate metabolism pathways. Collectively, this study provides valuable evidence on carbonate-responsive genes and insights into the different molecular mechanisms of saline and alkaline stresses.

Risk Factors for Mortality in Critically Ill Patients with Coagulation Abnormalities: A Retrospective Cohort Study.

OBJECTIVE: Coagulation abnormalities are common and prognostically significant in intensive care units (ICUs) and are associated with increased mortality. This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities. METHODS: This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022. The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0. Patients were followed up for 28 days, and multivariate logistic regression analysis was utilized to identify risk factors for mortality. RESULTS: Of the 451 patients analyzed, 115 died, and 336 were alive at the end of the 28-day period. Multivariate analysis revealed that elevated thrombin-antithrombin complex (TAT), tissue plasminogen activator inhibitor complex (tPAIC), prolonged prothrombin time, and thrombocytopenia were independent risk factors for mortality. For nonovert disseminated intravascular coagulation (DIC) patients, older age and thrombocytopenia were associated with increased risks of mortality, whereas elevated levels of plasmin α2-plasmin inhibitor complex (PIC) were found to be independent predictors of survival. In patients with overt DIC, elevated levels of tPAIC were independently associated with increased risks of mortality. Nevertheless, thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC. CONCLUSION: Coagulation markers such as the TAT, tPAIC, PIC, and platelet count were significantly associated with mortality, underscoring the importance of maintaining a balance between coagulation and fibrinolysis. These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.

Magnetite nanoparticles from representative coal fired power plants in China: Dust removal capture and their final atmospheric emission.

Information on the emission of coal combustion-sourced magnetite nanoparticles (MNPs) is lacking, which is critical for their health-related risks. In this study, MNPs in coal fly ashes (CFAs) from various coal-fired power plants (CFPPs) in China equipped with various dust removal devices were extracted and quantified using single particle ICP-MS. The number concentrations of MNPs in CFAs captured by dust removal increased with stage, while their size decreased. Among all the dust removal devices, electrostatic-fabric-integrated precipitators showed the best removal of MNPs. Furthermore, throughout all the coal combustion by-products in a typical CFPP, MNPs in EFA (fly ash escaped from the stack) showed the highest number concentration (1.2 × 107 particles/mg) and lowest size (78 nm). Although the mass of CFA escaping through the stack is extremely low, it still had an emission rate of 1.9 × 1015 particles/h, contributing 3.56 % of the total emissions of MNPs in number. In addition, the purity of MNPs and their associated toxic metals showed a size-dependent variation pattern. As the particle size of MNPs decreased, the proportion of Fe in MNPs increased from 43 % in bottom ash (BA) to 84 % in EFA, while the abundance of trace toxic metals in EFA was 3.3 times higher than that of BA. These MNPs with the highest purity can adsorb elevated concentrations of toxic metals, and can be discharged directly into the atmosphere, posing a risk of synergistic toxicity.

Post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation: a case report, meta-analysis, and systematic review.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

Case report: A therapeutic attempt to treat Morbihan disease with Baricitinib.

A woman in her thirties who had been diagnosed with Morbihan disease did not notice a significant improvement in her condition after receiving years of treatment. Our decision to use Baricitinib helped her to achieve a better outcome. To our knowledge, this is the first study to use Baricitinib in Morbihan disease, although JAK inhibitors have already been successfully used before. It is hoped that our case report will provide new treatment options for Morbihan disease therapy.

Establish a noninvasive model to screen metabolic dysfunction-associated steatotic liver disease in children aged 6-14 years in China and its applications in high-obesity-risk countries and regions.

Background: The prevalence of metabolic-associated steatotic liver disease (MASLD) is rising precipitously among children, particularly in regions or countries burdened with high prevalence of obesity. However, identifying those at high risk remains a significant challenge, as the majority do not exhibit distinct symptoms of MASLD. There is an urgent need for a widely accepted non-invasive predictor to facilitate early disease diagnosis and management of the disease. Our study aims to 1) evaluate and compare existing predictors of MASLD, and 2) develop a practical screening strategy for children, tailored to local prevalence of obesity. Methods: We utilized a school-based cross-sectional survey in Beijing as the training dataset to establish predictive models for screening MASLD in children. An independent school-based study in Ningbo was used to validate the models. We selected the optimal non-invasive MASLD predictor by comparing logistic regression model, random forest model, decision tree model, and support vector machine model using both the Beijing and Ningbo datasets. This was followed by serial testing using the best performance index we identified and indices from previous studies. Finally, we calculated the potential MASLD screening recommendation categories and corresponding profits based on national and subnational obesity prevalence, and applied those three categories to 200 countries according to their obesity prevalence from 1990 to 2022. Findings: A total of 1018 children were included (NBeijing = 596, NNingbo = 422). The logistic regression model demonstrated the best performance, identifying the waist-to-height ratio (WHtR, cutoff value ≥0.48) as the optimal noninvasive index for predicting MASLD, with strong performance in both training and validation set. Additionally, the combination of WHtR and lipid accumulation product (LAP) was selected as an optimal serial test to improve the positive predictive value, with a LAP cutoff value of ≥668.22 cm × mg/dL. Based on the obesity prevalence among 30 provinces, three MASLD screening recommendations were proposed: 1) "Population-screening-recommended": For regions with an obesity prevalence ≥12.0%, where MASLD prevalence ranged from 5.0% to 21.5%; 2) "Resources-permitted": For regions with an obesity prevalence between 8.4% and 12.0%, where MASLD prevalence ranged from 2.3% to 4.4%; 3) "Population-screening-not-recommended": For regions with an obesity prevalence <8.4%, where MASLD prevalence is difficult to detect using our tool. Using our proposed cutoff for screening MASLD, the number of countries classified into the "Population-screening-recommended" and "Resources-permitted" categories increased from one and 11 in 1990 to 95 and 28 in 2022, respectively. Interpretation: WHtR might serve as a practical and accessible index for predicting pediatric MASLD. A WHtR value ≥0.48 could facilitate early identification and management of MASLD in areas with obesity prevalence ≥12.0%. Furthermore, combining WHtR ≥0.48 with LAP ≥668.22 cm × mg/dL is recommended for individual MASLD screening. Moreover, linking these measures with population obesity prevalence not only helps estimate MASLD prevalence but also indicates potential screening profits in regions at varying levels of obesity risk. Funding: This study was supported by grants from Capital's Funds for Health Improvement and Research (Grant No. 2022-1G-4251), National Natural Science Foundation of China (Grant No. 82273654), Major Science and Technology Projects for Health of Zhejiang Province (Grant No. WKJ-ZJ-2216), Cyrus Tang Foundation for Young Scholar 2022 (2022-B126) and Sino-German Mobility Programme (M-0015).

Enabling Sustainable Ammonia Synthesis: From Nitrogen Activation Strategies to Emerging Materials.

Ammonia (NH3) is one of the most important precursors of various chemicals and fertilizers. Given that ammonia synthesis via the traditional Haber-Bosch process requires high temperatures and pressures, it is critical to explore effective strategies and catalysts for ammonia synthesis under mild reaction conditions. Although electrocatalysis and photocatalysis can convert N2 to NH3 under mild conditions, their efficiencies and production scales are still far from the requirements for industrialization. Thermal catalysis has been proven to be the most direct and effective approach for ammonia synthesis. Over the past few decades, significant efforts have been made to develop novel catalysts capable of nitrogen fixation and ammonia generation via thermal catalytic processes. In parallel with catalyst exploration, new strategies such as self-electron donation, hydride fixation, hydridic hydrogen reduction, and anionic vacancy promotion have also been explored to moderate the operating conditions and improve the catalytic efficiency of ammonia synthesis. In this review, the emergence of new materials and strategies for promoting N2 activation and NH3 formation during thermal catalysis is briefly summarized. Moreover, challenges and prospects are proposed for the future development of thermal catalytic ammonia synthesis.

[Cryoprotective effects of deicing micro/nanomaterials with different sizes and shapes on cells].

Extensive studies have been conducted on deicing nanomaterials to improve the cryoprotective effects on cells, tissues, and organs. The nanomaterials with different composition, sizes, and shapes can inhibit the formation and growth of ice crystals, thereby reducing the damage to the cryopreserved samples. In this study, the carbon composite particles (CCPs) with different sizes and shapes were prepared by the hydrothermal method. The results demonstrated that the cryoprotective effect of CCPs enhanced with the decrease in particle size. Compared with spherical CCPs, Janus nanoparticles and WSP nanoflower with special shapes demonstrated improved protective effects on cryopreserved cells. In addition, the combination of deicing micro/nanomaterials at appropriate concentrations with commercial cryoprotectants exerted improved cryoprotective effects on cells. The prepared deicing micro/nanomaterials can improve cell cryopreservation, demonstrating great application potential in biomedical research and cryopreservation.

Enhanced Immune Responses in Mice by Combining the Mpox Virus B6R-Protein and Aluminum Hydroxide-CpG Vaccine Adjuvants.

Novel adjuvants and innovative combinations of adjuvants (Adjuvant Systems) have facilitated the development of enhanced and new vaccines against re-emerging and challenging pathogenic microorganisms. Nonetheless, the efficacy of adjuvants is influenced by various factors, and the same adjuvant may generate entirely different immune responses when paired with different antigens. Herein, we combined the MPXV-B6R antigen with BC02, a novel adjuvant with proprietary technology, to assess its capability to induce both cellular and humoral immunity in mouse models. Mice received two intramuscular injections of B6R-BC02, which resulted in the production of MPXV-specific IgG, IgG1, and IgG2a antibodies. Additionally, it elicited strong MPXV-specific Th1-oriented cellular immunity and persistent effector memory B-cell responses. The advantages of BC02 were further validated, including rapid initiation of the immune response, robust recall memory, and sustained immune response induction. Although the potential of immunized mice to produce serum-neutralizing antibodies against the vaccinia virus requires further improvement, the exceptional performance of BC02 as an adjuvant for the MPXV-B6R antigen has been consistently demonstrated.

Gene Editing of the Endogenous Cryptic 3' Splice Site Corrects the RNA Splicing Defect in the ß654-Thalassemia Mouse Model.

ß654-thalassemia is caused by a point mutation in the second intron (IVS-II) of the ß-globin gene that activates a cryptic 3' splice site, leading to incorrect RNA splicing. Our previous study demonstrated that when direct deletion of the ß654 mutation sequence or the cryptic 3' splice site in the IVS-II occurs, correct splicing of ß-globin mRNA can be restored. Herein, we conducted an in-depth analysis to explore a more precise gene-editing method for treating ß654-thalassemia. A single-base substitution of the cryptic 3' acceptor splice site was introduced in the genome of a ß654-thalassemia mouse model using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9(Cas9)-mediated homology-directed repair (HDR). All of the HDR-edited mice allow the detection of correctly spliced ß-globin mRNA. Pathological changes were improved compared with the nonedited ß654 mice. This resulted in a more than twofold increase in the survival rate beyond the weaning age of the mice carrying the ß654 allele. The therapeutic effects of this gene-editing strategy showed that the typical ß-thalassemia phenotype can be improved in a dose-dependent manner when the frequency of HDR is over 20%. Our research provides a unique and effective method for correcting the splicing defect by gene editing the reactive splicing acceptor site in a ß654 mouse model.

Halogen Bond Unlocks Ultra-High Birefringence.

Anisotropy is crucial for birefringence (Δn) in optical materials, but optimizing it remains a formidable challenge (Δn >0.3). Supramolecular frameworks incorporating π-conjugated components are promising for achieving enhanced birefringence because of their structural diversity and inherent anisotropy. Herein, we first synthesized (C6H6NO2)+Cl- (NAC) and then constructed a halogen-bonded supramolecular framework I+(C6H4NO2)- (INA) by halogen aliovalent substitution of Cl- with I+. The organic moieties are protonated and deprotonated nicotinic acid (NA), respectively. The antiparallel arrangement of birefringent-active units in NAC and INA leads to significant differences in the bonding characteristics between the interlayer and intralayer domains. Moreover, the [O⋅⋅⋅I+⋅⋅⋅N] halogen bond in 1D [I+(C6H4NO2)-] chain exhibits stronger interactions and stricter directionality, resulting in a more pronounced in-plane anisotropy between the intrachain and interchain directions. Consequently, INA exhibits exceptional birefringent performance, with a value of 0.778 at 550 nm, twice that of NAC (0.363 at 550 nm). This value significantly exceeds those of commercial birefringent crystals, such as CaCO3 (0.172 at 546 nm), and is the highest reported value among ultraviolet birefringent crystals. This work presents a novel design strategy that employs halogen bonds as connection sites and modes for birefringent-active units, opening new avenues for developing high-performance birefringent crystals.

Polymeric microlens array formed on a discontinuous wetting surface using a self-assembly technique.

In this paper, we demonstrate a facile way to prepare polymeric microlens arrays (MLAs) based on a discontinuous wetting surface using a self-assembly technique. A patterned hydrophobic-octadecyltrichlorosilane (OTS) surface was prepared by U V/O 3 irradiation through a shadow mask. The area exposed to U V/O 3 irradiation turned highly hydrophilic, whereas the area protected by the mask remained highly hydrophobic, generating the patterned OTS surface. The surface energy of the OTS/glass surface changed from 23 to 72.8 mN/m after 17 min of U V/O 3 treatment. The scribing of the optical glue-NOA 81 onto the microhole array enabled one to obtain the MLAs due to the generation of the NOA 81 droplet array via the surface tension. After UV light curing, the cured NOA 81 droplet array with uniform dimensions within a large area exhibited excellent MLA characteristics. Moreover, the method developed in this study is simple in operation, low-cost, and requires neither a clean room nor expensive equipment.

Emergent normal fluid in the superconducting ground state of overdoped cuprates.

The microscopic mechanism for the disappearance of superconductivity in overdoped cuprates is still under heated debate. Here we use scanning tunneling spectroscopy to investigate the evolution of quasiparticle interference phenomenon in Bi2Sr2CuO6+δ over a wide range of hole densities. We find that when the system enters the overdoped regime, a peculiar quasiparticle interference wavevector with arc-like pattern starts to emerge even at zero bias, and its intensity grows with increasing doping level. Its energy dispersion is incompatible with the octet model for d-wave superconductivity, but is highly consistent with the scattering interference of gapless normal carriers. The gapless quasiparticles are mainly located near the antinodes and are independent of temperature, consistent with the disorder scattering mechanism. We propose that a branch of normal fluid emerges from the pair-breaking scattering between flat antinodal bands in the quantum ground state, which is the primary cause for the reduction of superfluid density and suppression of superconductivity in overdoped cuprates.

Complementary to Multiple Labels: A Correlation-Aware Correction Approach.

Complementary label learning (CLL) requires annotators to give irrelevant labels instead of relevant labels for instances. Currently, CLL has shown its promising performance on multi-class data by estimating a transition matrix. However, current multi-class CLL techniques cannot work well on multi-labeled data since they assume each instance is associated with one label while each multi-labeled instance is relevant to multiple labels. Here, we show theoretically how the estimated transition matrix in multi-class CLL could be distorted in multi-labeled cases as they ignore co-existing relevant labels. Moreover, theoretical findings reveal that calculating a transition matrix from label correlations in multi-labeled CLL (ML-CLL) needs multi-labeled data, while this is unavailable for ML-CLL. To solve this issue, we propose a two-step method to estimate the transition matrix from candidate labels. Specifically, we first estimate an initial transition matrix by decomposing the multi-label problem into a series of binary classification problems, then the initial transition matrix is corrected by label correlations to enforce the addition of relationships among labels. We further show that the proposal is classifier-consistent, and additionally introduce an MSE-based regularizer to alleviate the tendency of BCE loss overfitting to noises. Experimental results have demonstrated the effectiveness of the proposed method.

Ba2Ga2F6(IO3)(PO4): the first fluoride-containing iodate-phosphate with a 1D [Ga2F6(IO3)(PO4)]4- helix chain.

Herein, the first F-containing iodate-phosphate, namely Ba2Ga2F6(IO3)(PO4), was prepared via a hydrothermal reaction, in which HPF6 (70 wt% solution in water) was used as the source of both fluoride and phosphate anions for the first time. Ba2Ga2F6(IO3)(PO4) features an unprecedented 1D [Ga2F6(IO3)(PO4)]4- helix chain, composed of a 1D Ga(1)(IO3)O4F chain via the bridging of 0D Ga(2)(PO4)F5. The UV-Vis spectrum shows that Ba2Ga2F6(IO3)(PO4) has a wide bandgap with a short-UV absorption edge (4.35 eV; 253 nm). Birefringence measurement under a polarizing microscope shows that Ba2Ga2F6(IO3)(PO4) displays a moderate birefringence of 0.072@550 nm, which is consistent with the value (0.070@550 nm) obtained by DFT calculations, indicating that Ba2Ga2F6(IO3)(PO4) has potential applications as a short-UV birefringent material. This study highlights the crucial role played by the incorporation of specific functional groups into compounds, shedding light on their contribution to promising inorganic functional materials.

An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits.

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Macrophage polarization as a novel endpoint for assessing combined risk of phthalate esters.

Combined exposure to phthalate esters (PAEs) has garnered increasing attention due to potential synergistic effects on human health. This study aimed to develop an in vitro model using human macrophages to evaluate the combined toxicity of PAEs and explore the underlying mechanisms. A high-throughput screening system was engineered by expressing a PPRE-eGFP reporter in THP-1 monocytes to monitor macrophage polarization upon PAEs exposure. Individual PAEs exhibited varied inhibitory effects on M2 macrophage polarization, with mono(2-ethylhexyl) phthalate (MEHP) being the most potent. Isobologram analysis revealed additive interactions when MEHP was combined with other PAEs, resulting in more pronounced suppression of M2 markers compared to individual compounds. Mechanistic studies suggested PAEs may exert effects by modulating PPARγ activity to inhibit M2 polarization. Notably, an equimolar mixture of six PAEs showed additive inhibition of M2 markers. In vivo experiments corroborated the combined hepatotoxic effects, with mice exposed to a PAEs mixture exhibiting reduced liver weight, dyslipidemia, and decreased hepatic M2 macrophages compared to DEHP alone. Transcriptome analysis highlighted disruptions in PPAR signaling, and distinct pathway alterations on cholesterol metabolism in the mixture group. Collectively, these findings underscore the importance of evaluating mixture effects and provide a novel approach for hazard assessment of combined PAEs exposure with implications for environmental health risk assessment.

Establishment of human post-vaccination SARS-CoV-2 standard reference sera.

There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. IMPORTANCE: The explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.

A cocktail nanovaccine targeting key entry glycoproteins elicits high neutralizing antibody levels against EBV infection.

Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.