Self-Assembly of Glycolipid Epimers: Their Supramolecular Morphology Control and Immunoactivation Function.

Although advances have been made in carbohydrate-based macromolecular self-assembly, harnessing epimers of carbohydrates to perform molecular assembly and further investigating the properties of supramolecular materials remain little explored. Herein, two classes of stereoisomeric glycolipid amphiphiles based on d-N-acetylgalactosamine (GalNAc) are reported, and they can aggregate into ribbon-like structures in the aqueous solution due to amphiphilic property, which allow to obtain glycocalyx-mimicking supramolecular materials. The subtle distinction in glycoside configuration of GalNAc-α-SSA and GalNAc-ß-SSA dictates the different molecular packing in self-assembled structures. Since driven by the distinguishing carbohydrate-carbohydrate interactions, the ribbon-like architectures transform into spherical nanostructures via mixing GalNAc-α-SSA and GalNAc-ß-SSA. The resulting spherical micelles fabricated by blending glycolipid epimers can potentiate the macrophage- and dendritic cell-mediated immune responses in vitro. Such glycolipid epimers will pave the way to create glycocalyx-mimicking immune modulators by incorporating stereochemistry into supramolecular self-assembly.

Spatiotemporal Landscape for the Sophisticated Transformation of Protein Assemblies Defined by Multiple Supramolecular Interactions.

Precise protein assemblies not only constitute a series of living machineries but also provide an advanced class of biomaterials. Previously, we developed the inducing ligand strategy to generate various fixed protein assemblies, without the formation of noncovalent interactions between proteins. Here, we demonstrated that controlling the symmetry and number of supramolecular interactions introduced on protein surfaces could direct the formation of unspecific interactions between proteins and induce various nanoscale assemblies, including coiling nanowires, nanotubes, and nanosheets, without manipulation of the protein's native surfaces. More importantly, these nanoscale assemblies could spontaneously evolve into more ordered architectures, crystals. We further showed that the transformation from the introduced supramolecular interactions to the interactions formed between proteins was crucial for pathway selection and outcomes of evolution. These findings reveal a transformation mechanism of protein self-assembly that has not been exploited before and may provide an approach to generate complex and transformable biomacromolecular self-assemblies.

Oral voriconazole monotherapy for fungal keratitis: efficacy, safety, and factors associated with outcomes.

Purpose: To provide preliminary data on the efficacy and safety of oral voriconazole (VCZ) as a primary treatment for fungal keratitis (FK). Method: We performed a retrospective histopathological analysis of data on 90 patients with FK at The First Affiliated Hospital of Guangxi Medical University between September 2018 and February 2022. We recorded three outcomes: corneal epithelial healing, visual acuity (VA) improvement, and corneal perforation. Independent predictors were identified using univariate analysis, and multivariate logistic regression analysis was used to identify independent predictive factors associated with the three outcomes. The area under the curve was used to evaluate the predictive value of these factors. Results: Ninety patients were treated with VCZ tablets as the only antifungal drug. Overall, 71.1% (n = 64) of the patients had extreme corneal epithelial healing, 56.7% (n = 51) showed an improvement in VA, and 14.4% (n = 13) developed perforation during treatment. Non-cured patients were more likely to have large ulcers (≥5 × 5 mm2) and hypopyon. Conclusion: The results indicated that oral VCZ monotherapy was successful in the patients with FK in our study. Patients with ulcers larger than 5 × 5 mm2 and hypopyon were less likely to respond to this treatment.

Nanovaccine Based on a Biepitope Antigen to Potentiate the Immunogenicity of a Neoantigen.

Specific neoantigens are promising candidates for personalized cancer vaccines and immunotherapies, whereas the low immunogenicity and physicochemical variability are the main challenges in clinical trials. Herein, based on the rational design of neoantigens, we developed biepitope nanovaccines via integrating CD4+ with CD8+ T cell epitopes. A class of amphiphilic peptides composed of biepitope and hydrophilic amino acids can form well-defined nanostructures, thus incorporating functional sequences into an artificial platform. Cellular uptake studies demonstrated the enhanced endocytosis of biepitope neoantigens in dendritic cells (DCs). Such designed biepitopes can further stimulate the maturation of DCs, as validated by the upregulation of costimulatory molecules and secreted proinflammatory cytokines, which show the potential ability to prime T cells and evoke specific cellular immunity. The inspiring prophylactic and therapeutic efficacy of biepitope nanovaccines was evaluated in murine colon cancer. In contrast to individual CD8+ T cell epitopes, the rationally designed biepitope nanovaccines can efficiently provoke immune activation and potentiate antitumor immunity both in vitro and in vivo, presenting an alternative strategy for neoantigen vaccines.

Global trends and prospects in research of artificial cornea over past 20 years: a bibliometric and visualized analysis.

BACKGROUND: Many studies have been focused on the area of the artificial cornea. In our study, a bibliometric analysis was performed on the artificial cornea to identify the global key research fields and trends over the past 20 years. METHODS: Publications about artificial cornea were retrieved and downloaded from the Web of Science Core Collection from 2002 to 2021. CiteSpace and VOSviewer were used to analyze countries, institutions, authors, and related research areas. RESULTS: A total of 829 eligible publications were analyzed. The USA was the most productive country for the artificial cornea, followed by China and Canada. Harvard University was the most prolific institution in this field. Cornea published most of the studies in this area and Dohlman CH was the most cited author. CONCLUSIONS: Bibliometric analysis in our study first provides a general perspective on the artificial cornea, which can be helpful to further explore the issues in the rapidly developing area.

Engineering single-atom Fe-Pyridine N4 sites to boost peroxymonosulfate activation for antibiotic degradation in a wide pH range.

Single-atom Fe catalysts have shown great potential for Fenton-like technology in organic pollutant decomposition. However, the underlying reaction pathway and the identification of Fe active sites capable of activating peroxymonosulfate (PMS) across a wide pH range remain unknown. We presented a novel strategy for deciphering the production of singlet oxygen (1O2) by regulating the Fe active sites in this study. Fe single atoms loaded on nitrogen-doped porous carbon (FeSA-CN) catalysts were synthesized using a cage encapsulation method and compared to Fe-nanoparticle-loaded catalysts. It was discovered that FeSA-CN catalysts served as efficient PMS activators for pollutant decomposition over a wide pH range. Several analytical measurements and density functional theory calculations revealed that the pyridinic N-ligated Fe single atom (Fe-pyridine N4) was involved in the production of 1O2 by the binding of two PMS ions, resulting in an excellent catalytic performance for PMS adsorption/activation. This work has the potential to not only improve the understanding of nonradical reaction pathway but to also provide a generalizable method for producing highly stable PMS activators with high activity for practical wastewater treatment.

Carbohydrate-Based Macromolecular Biomaterials.

Carbohydrates are the most abundant and one of the most important biomacromolecules in Nature. Except for energy-related compounds, carbohydrates can be roughly divided into two categories: Carbohydrates as matter and carbohydrates as information. As matter, carbohydrates are abundantly present in the extracellular matrix of animals and cell walls of various plants, bacteria, fungi, etc., serving as scaffolds. Some commonly found polysaccharides are featured as biocompatible materials with controllable rigidity and functionality, forming polymeric biomaterials which are widely used in drug delivery, tissue engineering, etc. As information, carbohydrates are usually referred to the glycans from glycoproteins, glycolipids, and proteoglycans, which bind to proteins or other carbohydrates, thereby meditating the cell-cell and cell-matrix interactions. These glycans could be simplified as synthetic glycopolymers, glycolipids, and glycoproteins, which could be afforded through polymerization, multistep synthesis, or a semisynthetic strategy. The information role of carbohydrates can be demonstrated not only as targeting reagents but also as immune antigens and adjuvants. The latter are also included in this review as they are always in a macromolecular formulation. In this review, we intend to provide a relatively comprehensive summary of carbohydrate-based macromolecular biomaterials since 2010 while emphasizing the fundamental understanding to guide the rational design of biomaterials. Carbohydrate-based macromolecules on the basis of their resources and chemical structures will be discussed, including naturally occurring polysaccharides, naturally derived synthetic polysaccharides, glycopolymers/glycodendrimers, supramolecular glycopolymers, and synthetic glycolipids/glycoproteins. Multiscale structure-function relationships in several major application areas, including delivery systems, tissue engineering, and immunology, will be detailed. We hope this review will provide valuable information for the development of carbohydrate-based macromolecular biomaterials and build a bridge between the carbohydrates as matter and the carbohydrates as information to promote new biomaterial design in the near future.

Complex effects of pH and organic shocks on arsenic oxidation and removal by manganese-oxidizing aerobic granular sludge in sequencing batch reactors.

Biological technologies are efficient and economical methods for removing toxic arsenic (As) from organic wastewaters. In this study, four sequencing batch reactors of manganese-oxidizing aerobic granular sludge (Mn-AGS) were operated in duplicate and imposed with acidic pH and high organic shocks. Batch experiments with different initial conditions were conducted to investigate the effects of pH and organic load on As(III) oxidation and removal. The results indicate that acidic pH shocks (influent pH decreased to 4.0/3.0) unexpectedly increased the As removal efficiency from 23.4-38.2% to 64.7-72.5%. The effects of high organic shocks were very complicated, as the results of the shocks were opposite twice. According to the results of the batch experiments, it was estimated that the suitable pH range for high performance was 5.0-8.5 in reaction liquid. Although acidic pH shocks initially inhibited As(III) oxidation and removal, they largely extended the reaction time of the suitable pH range and finally improved the As removal efficiency. There were many negative and positive factors affecting the As removal during the high organic shocks, leading to the unstable responses. Moreover, the microbial community was not largely changed by pH or organic shocks, and genus Hydrogenophaga (∼8%) might be responsible for the microbial As(III) oxidation. Finally, several operation strategies were proposed to obtain high performance, such as liquid pH control and aeration improvement.

Incorporating Lanthanum into Mesoporous Silica Foam Enhances Enzyme Immobilization and the Activity of Penicillin G Acylase Due to Lewis Acid-Base Interactions.

Penicillin G acylase (PGA) has been immobilized on a lanthanum-incorporated mesostructured cellular foam (La-MCF) support by using the interaction between the strong Lewis acid sites on the surface of La-MCF and the free amino groups of lysine residues of PGA. The La-MCF support was successfully synthesized in situ through the addition of a citric acid (CA) complexant. The results of pyridine-IR spectroscopy show the presence of strong Lewis acid sites on the surface of the prepared La-MCF (with CA), attributed to the incorporation of lanthanum species into the framework of MCF. Through interaction with the strong Lewis acid sites, the enzymes can be firmly immobilized on the surface of the support. The results indicate that PGA/La-MCF (with CA) exhibits a high specific activity and greatly enhanced operational stability. For the hydrolysis of penicillin G potassium salt, the initial specific activity of PGA/La-MCF (with CA) reaches 10023 U/g. Even after being recycled 10 times, PGA/La-MCF (with CA) retains 89 % of its initial specific activity, much higher than the 77 % of PGA/Si-MCF.

Self-Assembled Saccharide-Functionalized Amphiphilic Metallacycles as Biofilms Inhibitor via "Sweet Talking".

Bacterial biofilms are troublesome in the treatment of bacterial infectious diseases due to their inherent resistance to antibiotic therapy. Exploration of alternative antibiofilm reagents provides opportunities to achieve highly effective treatments. Herein, we propose a strategy to employ self-assembled saccharide-functionalized amphiphilic metallacycles ([2+2]-Gal, [3+3]-Gal, and [6+6]-Gal) with multiple positive charges as a different type of antibacterial reagent, marrying saccharide functionalization that interact with bacteria via "sweet talking". These self-assembled glyco-metallacycles gave various nanostructures (nanoparticles, vesicles or micron-sized vesicles) with different biofilms inhibition effect on Staphylococcus aureus (S. aureus). Especially, the peculiar self-assembly mechanism, superior antibacterial effect and biofilms inhibition distinguished the [6+6]-Gal from other metallacycles. Meanwhile, in vivo S. aureus pneumonia animal model experiments suggested that [6+6]-Gal could relieve mice pneumonia aroused by S. aureus effectively. In addition, the control study of metallacycle [3+3]-EG5 confirmed the significant role of galactoside both in the self-assembly process and the antibacterial efficacy. In view of the superior effect against bacteria, the saccharide-functionalized metallacycle could be a promising candidate as biofilms inhibitor or treatment agent for pneumonia.

Morphology separation in ghost imaging via sparsity constraint.

The separation of morphology components in ghost imaging via sparsity constraint is investigated by adapting the morphology component analysis technique based on the fact that different morphology components can be sparsely expressed in different basis. The successful separation of reconstructed image plays an important role in the ability to identify it, analyze it, enhance it and more. This approach is first studied with numerical simulations and then verified with both table-top and outdoor experimental data. Results show that it can not only separate different morphology components but also improve the quality of the reconstructed image.