Porous reticular Co@Fe metal-organic gel: dual-function simulated peroxidase nanozyme for both colorimetric sensing and antibacterial applications.

Constructing metal-organic gels (MOGs) with enzyme-catalyzed activity and studying their catalytic mechanism are crucial for the development of novel nanozyme materials. In this study, a Co@Fe MOG with excellent peroxidase activity was developed by a simple and mild one-pot process. The results showed that the material exhibited almost a single peroxidase activity under optimal pH conditions, which allowed it to attract and oxidize the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB). Based on the active electron transfer between the metal centers and the organic ligand in the synthetic material, the Co@Fe MOG-H2O2-TMB system was verified to be able to detect H2O2 and citric acid (CA). The catalytic microenvironment formed by the adsorption and the catalytic center accelerated the electron-transfer rate, which expedited the generation of hydroxyl radicals (˙OH, a kind of reactive oxygen species (ROS)) in the presence of H2O2. The persistence and high intensity of ˙OH generation were proven, which would endow Co@Fe MOG with a certain antibacterial ability, promoting the healing of bacteria-infected wounds. In conclusion, this study contributes to the development efforts toward the application systems of nanozymes for marker detection and antibacterial activity.

Applications of cerium-based materials in food monitoring.

With the rapid development of society, food safety to public health has been a topic that cannot be ignored. In recent years, lanthanide-based materials are studied to be potential candidates in the detection of food samples. Cerium (Ce)-based materials (such as Ce ions, CeO2, Ce-metal organic framework (Ce-MOF), etc.) have also attracted more attention in food detection by virtue of colorimetric, fluorescence, sensing, and other methods. This is because the mixed valence of Ce (Ce3+ and Ce4+), the formation of oxygen vacancies, and their optical and electrochemical properties. In this review, Ce-based materials will be introduced and discussed in the field of food detection, including biogenesis, construction, catalytic mechanisms, combination, and applications. In addition, the current challenges and future development trend of these Ce-based materials in food safety detection are also proposed and discussed. Therefore, it is meaningful to explore the Ce-based materials for detection of biomarkers in food samples.

Applications of microalga-powered microrobots in targeted drug delivery.

Over the past decade, researchers have proposed a new class of drug delivery systems, bio-hybrid micro-robots, designed with a variety of living cell-driven micro-robots that utilize the unique mobility of natural organisms (bacteria, cells, exosomes, etc.) to transport effective drugs. Microalgae are considered potential drug delivery carriers. Recent studies have shown that microalga-based drug delivery systems exhibit excellent biocompatibility. In addition, microalgae have a large surfactant area, phototaxis, oxygen production, and other characteristics, so they are used as a carrier for the treatment of bacterial infections, cancer, etc. This review summarizes the modification of microalgae including click chemistry and electrostatic adsorption, and can improve the drug loading efficiency through dehydration and hydration strategies. The prepared microalgal drug delivery system can be targeted to different organs by different dosing methods or using external forces. Finally, it summarizes its antibacterial (gastritis, periodontitis, skin wound inflammation, etc.) and antitumor applications.

Rapidly separable microneedle patch for the controlled and sustained release of 5-fluorouracil.

5-Fluorouracil (5-FU) is frequently used in the treatment of tumors and swollen tissues. However, traditional administration methods can result in poor patient compliance and require to administrate frequently due to the short T1/2 of 5-FU. Herein, the 5-FU@ZIF-8 loaded nanocapsules were prepared using multiple emulsion solvent evaporation methods to enable the controlled and sustained release of 5-FU. To decrease the drug release rate and enhance patient compliance, the obtained pure nanocapsules were added to the matrix to fabricate rapidly separable microneedles (SMNs). The entrapment efficiency (EE%) of 5-FU@ZIF-8 loaded nanocapsules was in the range of 41.55-46.29 %, and the particle size of ZIF-8, 5-FU@ZIF-8, and 5-FU@ZIF-8 loaded nanocapsules were 60 nm, 110 nm, and 250 nm respectively. According to the release study in vivo and in vitro, we concluded that 5-FU@ZIF-8 nanocapsules could achieve the sustained release of 5-FU and that the burst release of nanocapsules could be elegantly handled by incorporating nanocapsules into the SMNs. What's more, the use of SMNs could improve patient compliance due to the rapid separation of needles and backing of SMNs. The pharmacodynamics study also revealed that the formulation would be a better choice for the treatment of scars due to the advantages of painlessness, separation ability, and high delivery efficiency. In conclusion, the SMNs containing 5-FU@ZIF-8 loaded nanocapsules could serve as a potential strategy for some skin diseases therapy with controlled and sustained drug release behavior.

Molecular mechanism of antibody neutralization of coxsackievirus A16.

Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies.

Neutralizing Potency of Prototype and Omicron RBD mRNA Vaccines Against Omicron Variant.

The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD). Consequently, Omicron is able to extensively escape existing neutralizing antibodies and may therefore compromise the efficacy of current vaccines based on the original strain, highlighting the importance and urgency of developing effective vaccines against Omicron. Here we report the rapid generation and evaluation of an mRNA vaccine candidate specific to Omicron, and explore the feasibility of heterologous immunization with WT and Omicron RBD vaccines. This mRNA vaccine encodes the RBD of Omicron (designated as RBD-O) and is formulated with lipid nanoparticle. Two doses of the RBD-O mRNA vaccine efficiently induce neutralizing antibodies in mice; however, the antisera are effective only on the Omicron variant but not on the wildtype and Delta strains, indicating a narrow neutralization spectrum. It is noted that the neutralization profile of the RBD-O mRNA vaccine is opposite to that observed for the mRNA vaccine expressing the wildtype RBD (RBD-WT). Importantly, booster with RBD-O mRNA vaccine after two doses of RBD-WT mRNA vaccine can significantly increase neutralization titers against Omicron. Additionally, an obvious increase in IFN-γ, IL-2, and TNF-α-expressing RBD-specific CD4+ T cell responses was observed after immunization with the RBD-WT and/or RBD-O mRNA vaccine. Together, our work demonstrates the feasibility and potency of an RBD-based mRNA vaccine specific to Omicron, providing important information for further development of heterologous immunization program or bivalent/multivalent SARS-CoV-2 vaccines with broad-spectrum efficacy.

Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection.

Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.

Facilitation effect of incidental environmental context on the computer screen for paired-associate learning.

Three experiments, in which a total of 198 undergraduates engaged, investigate whether the incidental environmental context on the computer screen influences paired-associate learning. Experiment 1 compared the learning of foreign- and native-language words between a constant context condition, where the stimulus and response pairs were presented twice on the same 5-s video background context, and a varied context condition, where the pairs were presented twice on different video contexts. Repetition in the same context resulted in better learning than in different contexts, evaluated with a paper-and-pencil test. Experiment 2 investigated learning of paired-associate foreign and native words in the same video contexts, or photograph contexts, or on a neutral grey background. Both the video and the photograph contexts equally facilitated the paired-associate learning compared with the grey background. Experiment 3 investigated whether the incidental environmental context similarly facilitated face-name paired-associate learning. We added a new condition of spot illustrations, and a second testing 1 day later. The repetition of face-name pairs within the same complex incidental environmental context on the computer screen (either video or photograph background) facilitated the paired-associate learning. There was no significant difference in learning performance between video and photograph background contexts, which were significantly better than grey or spot-illustration backgrounds which did not differ from each other. The retention interval did not interact with the effect of the background. The present results show that repetition within the same video or photograph context, covering the entire background of the video screen on which each item pair was superimposed, facilitates paired-associate learning.