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Nano/microparticles are widely used as vaccine adjuvants to improve antigen stability and enhance immune response. Conformational stability of a given protein was normally assessed using differential scanning calorimetry (DSC) for the optimization of formulation and for ensuring antigen stability in vaccine products. Here, a higher throughput version, namely the microtiter plate-based differential scanning fluorimetry (DSF) method was developed and optimized for assessing the protein thermal stability in the particulate adjuvant-adsorbed form. Using recombinant human papillomavirus (HPV) vaccine antigens, along with several model proteins, enhanced sensitivity and correlation to the well-established differential scanning calorimetry were demonstrated. Higher throughput and much smaller sample consumption (1/10 ∼ 1/20 of the amount needed as compared to DSC) make the plate-based DSF a method of choice for formulation development, particularly during the early developmental phase of a project where the sample amount is usually quite limited.

A thorough understanding of the cell behaviors of the human neural grafts is fundamental to exploit them to achieve cell therapy for recovering brain functions. Here by using immunohistological staining, we trace the cell fate of the intrastriatal human neural progenitor cell (NPC) grafts up to 9 months in adult rats, with multiple examining time points to provide a unified working time frame for future transplantation study. Lots of Nestin+/Sox2+ human cells continuously migrate along the white matter tracts into distal brain parenchyma even long time after transplantation, providing a potential for curing diffuse brain damage. Further analysis reveals a significant heterogeneity of the long-term sustained neural stem cells (NSC)/NPCs that progressing throughout different stages, mimicking the neural development of human forebrain. More importantly, the initial GFAP expression in human grafts marks the NSC progression instead of terminal astrocyte differentiation. The distally migrating human cells continuously show the capability to produce new neurons, albeit at a low efficiency in the intact brain. Further investigations in neural disease models are needed. Such study would benefit neural cell therapy with regarding to the optimization of the transplantation strategy and choosing of acting mode by neural grafts (e.g. via cell replacement orex vivogene therapy).

Quantum Bell nonlocality is an important quantum phenomenon. Recently, the shareability of Bell nonlocality under unilateral measurements has been widely studied. In this study, we consider the shareability of quantum Bell nonlocality under bilateral measurements. Under a specific class of projection operators, we find that quantum Bell nonlocality cannot be shared for a limited number of times, as in the case of unilateral measurements. Our proof is analytical and our measurement strategies can be generalized to higher dimension cases., Comment: 15 pages

Both electrolytic manganese solid waste (EMSW) and phosphogypsum (PG) are solid waste that can cause serious pollution to the environment. Therefore, we try to solidify/stabilize heavy metal ions without adding other curing agents. We found that the Mn2+, Ni2+, Zn2+, Pb2+ and Cd2+ concentrations are 2432.00, 1.47, 3.80, 0.22 and 0.06 mg/L in the EMSW liquid leaching, and 0.26, 2.14, 8.62, 2.79 and 0.57 mg/L in the PG liquid leaching. The optimum conditions for synergistic stabilization/solidification are as follows: The ratio of EMSW to PG is 1:3, the stirring time is 2 h, and the solid–liquid ratio is 1:5. Under these conditions, the Mn2+, Ni2+, Zn2+, Pb2+ and Cd2+ concentrations in leaching liquid were reduced to 599.10, 0.33, 0.56, 0.06 and 0.01 mg/L, and the corresponding curing rates were 75.37%, 77.79%, 85.39%, 72.52% and 77.61%, respectively. When the Ni2+, Zn2+, Cu2+, Pb2+ and Cd2+ concentrations were within the permitted level for the GB8978-1996 test suggested by China’s environmental protection law, the residual manganese content in the leaching liquid of cured EMSW was too high to reach the emission standard. This work indicates that the synergistic stabilization/solidification of heavy metal ions has certain application potential.

Alkyl amines are surfactants used as quartz collectors in the reverse flotation of phosphate ores. It is important in both research and industrial practice to quantify amine concentration in the solution and/or wastewater. A simple and rapid method using high-performance liquid chromatography (HPLC) was developed to quantitatively determine the concentration of amine collectors (including dodecylamine, tetradecylamine, hexadecylamine, and octadecylamine) in a mineral flotation system. The method involved a sample derivatization procedure with 9-fluorenyl methoxycarbonyl chloride (FMOC-Cl) and separation/determination by HPLC coupled with a fluorescence detector. The calibration curves showed good linearity (R2 > 0.9956) in the range of 0.20–5.00 µg/mL, and the recoveries of dodecylamine, tetradecylamine, hexadecylamine, and octadecylamine were in the ranges of 84.93–97.64%, 89.93–101.92%, 85.29–98.37%, and 93.57–103.26%, respectively. The method was successfully used to quantify amines in wastewater from flotation experiments and artificial flotation wastewater (amine solution after activated carbon adsorption). The results from the analysis of four amines in the solution demonstrated that the proposed method is suitable for the simultaneous determination of amines in flotation pulp and wastewater.

Red mud (RM) is a hazardous solid waste discharged from the alumina production process. The stock of RM is very large, and it has strong alkalinity and certain radioactivity, which makes it have a very serious adverse effect on the environment. Many scholars have carried out extensive experimental investigations on the minimization, hazard-free treatment, and reutilization of RM, and encouraging results have been obtained. However, reutilization of RM has been restricted mainly due to its complex composition and strong alkalinity. In this study, carbide slag, a byproduct of acetylene production, was utilized to remove alkalis (Na

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both TH1- and TH2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.

Aim: Traditional antigenicity assay requires antigen recovery from the particulate adjuvants prior to analysis. An in situ method was developed for interrogating vaccine antigens with monoclonal antibodies while being adsorbed on adjuvants. Materials & methods: The fluorescence imaging-based high content analysis was used to visualize the antigen distribution on adjuvant agglomerates and to analyze the antigenicity for adsorbed antigens. Results: Simultaneous visualization and quantitation were achieved for dual antigens in a bivalent human papillomavirus vaccine with uniquely labeled antibodies. Good agreement was observed between the in situ multiplexed assays with well-established sandwich enzyme-linked immunosorbent assays. Conclusion: The streamlined procedures and the amenability for multiplexing make the in situ antigenicity analysis a favorable choice for in vitro functional assessment of bionanoparticles as vaccine antigens.

To determine the level of bone metabolism indexes in patients with chronic obstructive pulmonary disease and its clinical significance. A total of 164 patients with chronic obstructive pulmonary disease admitted to the outpatient and inpatient departments of our hospital from April 2019 to April 2020 were selected as the study objects. Patients were divided into acute exacerbation group (n=78) and remission group (n=52) according to relevant criteria in chronic obstructive pulmonary disease. There was no significant difference in gender, age, body mass index and other general data among the three groups (p>0.05), showing comparability. The bone mineral density of femoral neck, lumbar spine and Ward’s triangle in the three groups had statistical significance (p

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

The monogamy relations satisfied by quantum correlation measures play important roles in quantum information processing. Generally they are given in summation form. In this note, we study monogamy relations in product form. We present product-form monogamy relations for Bell nonlocality for three-qubit and multi-qubit quantum systems. We then extend our studies to other quantum correlations such as concurrence., 5 pages

We study the trade-off relations on the maximal violation of CHSH tests for the multi-qubit pure states. Firstly, according to the classification of 3-qubit pure states under stochastic local operations and classical communication, four trade-off relations on CHSH tests are provided. The process of proof also provides the method of calculating its exact value. Then we consider the multi-qubit quantum systems, and we prove that the conjecture in [PRA 94, 042105 (2016)] is right for some special 4-qubit or more qubit pure states., 10pages

Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins—receptor binding domain (RBD), S1 subunit and S ectodomain—in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 Å proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.

Thimerosal has been widely used as a preservative in drug and vaccine products for decades. Due to the strong propensity to modify thiols in proteins, conformational changes could occur due to covalent bond formation between ethylmercury (a degradant of thimerosal) and thiols. Such a conformational change could lead to partial or even complete loss of desirable protein function. This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus (HPV) 18 virus-like particles (VLPs). Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed. Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration. Two highly neutralizing antibodies, 13H12 and 3C3, were found to be the most sensitive to thimerosal treatment. The kinetics of antigenicity loss, when monitored with 13H12 or 3C3 as probes, yielded two distinctly different sets of kinetic parameters, while the data from both monoclonal antibodies (mAbs) followed a biphasic exponential decay model. The potential effect of thimerosal on protein function, particularly for thiol-containing proteinaceous active components, needs to be comprehensively characterized during formulation development when a preservative is necessary., Graphical abstract Image 1, Highlights • Altered antigenicity of thimerosal-treated HPV VLPs was observed with antibodies. • Antigenicity reduction and capsid destabilization were concentration dependent. • The kinetics of epitope-specific antigenicity loss were monitored in real time. • The reduced antigenicity of adjuvant-adsorbed antigens was visualized.

We study the trade-off relations given by the l_1-norm coherence of general multipartite states. Explicit trade-off inequalities are derived with lower bounds given by the coherence of either bipartite or multipartite reduced density matrices. In particular, for pure three-qubit states, it is explicitly shown that the trade-off inequality is lower bounded by the three tangle of quantum entanglement., 6 pages

The current coronavirus disease 2019 (COVID-19) pandemic was the result of the rapid transmission of a highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is no efficacious vaccine or therapeutic. Toward the development of a vaccine, here we expressed and evaluated as potential candidates four versions of the spike (S) protein using an insect cell expression system: receptor binding domain (RBD), S1 subunit, the wild-type S ectodomain (S-WT), and the prefusion trimer-stabilized form (S-2P). We showed that RBD appears as a monomer in solution, whereas S1, S-WT, and S-2P associate as homotrimers with substantial glycosylation. Cryo-electron microscopy analyses suggested that S-2P assumes an identical trimer conformation as the similarly engineered S protein expressed in 293 mammalian cells but with reduced glycosylation. Overall, the four proteins confer excellent antigenicity with convalescent COVID-19 patient sera in enzyme-linked immunosorbent assay (ELISA), yet show distinct reactivities in immunoblotting. RBD, S-WT and S-2P, but not S1, induce high neutralization titres (>3-log) in mice after a three-round immunization regimen. The high immunogenicity of S-2P could be maintained at the lowest dose (1 μg) with the inclusion of an aluminium adjuvant. Higher doses (20 μg) of S-2P can elicit high neutralization titres in non-human primates that exceed 40-times the mean titres measured in convalescent COVID-19 subjects. Our results suggest that the prefusion trimer-stabilized SARS-CoV-2 S-protein from insect cells may offer a potential candidate strategy for the development of a recombinant COVID-19 vaccine.

Hepatitis E virus (HEV) infection causes sporadic outbreaks of acute hepatitis worldwide. HEV was previously considered to be restricted to resource-limited countries with poor sanitary conditions, but increasing evidence implies that HEV is also a public health problem in developed countries and regions. Fortunately, several vaccine candidates based on virus-like particles (VLPs) have progressed into the clinical development stage, and one of them has been approved in China. This review provides an overview of the current HEV vaccine pipeline and future development with the emphasis on defining the critical quality attributes for the well-characterized vaccines. The presence of clinically relevant epitopes on the VLP surface is critical for eliciting functional antibodies against HEV infection, which is the key to the mechanism of action of the prophylactic vaccines against viral infections. Therefore, the epitope-specific immunochemical assays based on monoclonal antibodies (mAbs) for HEV vaccine antigen are critical methods in the toolbox for epitope characterization and for in vitro potency assessment. Moreover, serological evaluation methods after immunization are also discussed as biomarkers for clinical performance. The vaccine efficacy surrogate assays are critical in the preclinical and clinical stages of VLP-based vaccine development.

In this paper, we use certain norm inequalities to obtain new uncertain relations based on the Wigner-Yanase skew information. First for an arbitrary finite number of observables we derive an uncertainty relation outperforming previous lower bounds. We then propose new weighted uncertainty relations for two noncompatible observables. Two separable criteria via skew information are also obtained., Comment: 11pages

We study the uncertainty relation in the product form of variances and obtain some new uncertainty relations with weight, which are shown to be tighter than those derived from the Cauchy Schwarz inequality., Comment: 6 pages,1 figure

Human papillomavirus (HPV) type 16 is the most common type implicated as the etiological agent that causes cervical cancer. The marketed prophylactic vaccines against HPV infection are composed of virus-like particles (VLPs) assembled from the recombinant major capsid protein L1. Elicitation of functional and neutralizing antibodies by vaccination is the mode of action by which the vaccines prevent the viral infection. In this study, a panel of murine mAbs against HPV16 L1 were generated and comprehensively characterized with respect to their mapping to the epitope spectrum on the viral capsid. These mAbs were categorized into five epitope bins by two different methods based on the pairwise cross-inhibition and competition with human polyclonal antibodies. In addition, a preliminary demonstration of the spatial relationship of the epitopes recognized by these mAbs was performed using a cross-blocking assay with a well-characterized human mAb, 26D1. Interestingly, two mAbs recognizing different epitopes were found to act synergistically in the pseudovirion-based neutralization assay (PBNA). To facilitate cross-lab and cross-study comparison, the international standard (IS) serum 05/134 was used to calibrate the mAbs as well as the human serum samples from the HPV16/18 vaccine recipients. The neutralizing mAbs, particularly those that recognizing immunodominant epitopes, would be useful in developing epitope-specific assays for monitoring the vaccine production process and for serological assessment.

In this work, we predicted three new two-dimensional (2D) Be2C structures, namely, α-Be2C, β-Be2C, and γ-Be2C, on the basis of density functional theory (DFT) computations and the particle-swarm optimization (PSO) method. In α-Be2C, a carbon atom binds to eight Be atoms, forming an octacoordinate carbon moiety. This is the first example of an octacoordinate carbon containing material. The other two structures, β-Be2C and γ-Be2C, are quasi planar hexacoordinate carbon (phC) containing 2D materials. Good stability with these three phases is revealed by their lower cohesive energy and positive phonon modes. More interestingly, these predicted new phases of Be2C are all semiconductors and have unusual negative Poisson’s ratios (NPRs). If synthesized, 2D Be2C materials will have a broad range of applications in electronics and mechanics.

We study the equivalence of mixed states under local unitary transformations. First we express quantum states in Bloch representation. Then based on the coefficient matrices, some invariants are constructed. This method and results can be extended to multipartite high dimensional system., 10pages