暂无摘要。

Shigellosis, an acute gastroenteritis infection caused by Shigella species, remains a public health burden in developing countries. Recently, many outbreaks due to Shigella sonnei multidrug-resistant strains have been reported in high-income countries, and the lack of an effective vaccine represents a major hurdle to counteract this bacterial pathogen. Vaccine candidates against Shigella sonnei are under clinical development, including a Generalized Modules for Membrane Antigens (GMMA)-based vaccine. The mechanisms by which GMMA-based vaccines interact and activate human immune cells remain elusive. Our previous study provided the first evidence that both adaptive and innate immune cells are targeted and functionally shaped by the GMMA-based vaccine. Here, flow cytometry and confocal microscopy analysis allowed us to identify monocytes as the main target population interacting with the S. sonnei 1790-GMMA vaccine on human peripheral blood. In addition, transcriptomic analysis of this cell population revealed a molecular signature induced by 1790-GMMA mostly correlated with the inflammatory response and cytokine-induced processes. This also impacts the expression of genes associated with macrophages\' differentiation and T cell regulation, suggesting a dual function for this vaccine platform both as an antigen carrier and as a regulator of immune cell activation and differentiation.

The identification of weak-affinity ligands targeting membrane proteins is of great interest in Fragment-Based Drug Design (FBDD). Recently, miniaturized weak affinity chromatography (WAC) has been proposed as a valuable tool to study interactions between small ligands and wild-type membrane proteins embedded in so-called nanodisc biomimetic membranes immobilized on GMA-co-EDMA monoliths in situ-synthesized in capillary columns (less than one microliter in volume). In this proof-of-concept study, the achievable affinity range was limited to medium affinity (low micromolar range). The present work investigates different strategies to extend the affinity range towards low affinities, either by increasing the density of membrane proteins on the chromatographic support or by reducing non-specific interactions with the monolith. The combination of the use of a new and more hydrophilic monolithic support (poly(DHPMA-co-MBA)) and a multilayer nanodisc grafting process (up to three layers) allows a significant increase in the membrane protein density by a more than three-fold factor (up to 5.4 pmol cm-1). Such an increase in protein density associated with reduced non-specific interactions makes it possible to extend the range of detectable affinity, as demonstrated by the identification and characterization of affinities of very low-affinity ligands (Kd values of several hundred micromolar) for the adenosine receptor AA2AR used as a model protein, which was not possible before. The affinity was confirmed by competition experiments.

Introduction: Tissue conditioners have been widely used in various clinical applications in dentistry, such as treating inflamed alveolar ridges, temporarily relining partial and complete dentures, and the acquisition of functional impressions for denture fabrication. This study aimed to investigate the mechanical properties of the most prevalent tissue conditioner materials on the market, including Tissue Conditioners (TC), Visco Gel (VG), and FITT (F). Materials and Methods: The three tissue conditioners, TC, VG, and F, were assessed based on the parameters mentioned above. The following tests were performed based on the ISO 10139-1 and ISO 10139-2 requirements: Shore A hardness, denture plate adhesion, sorption, water solubility, and contraction after 1 and 3 days in water. Additional tests are described in the literature, such as ethanol content and gelling time. The tests were carried out by storing the materials in water at 37 °C for 7 days. Results: The gel times of all tested materials exceeded 5 min (TC = 300 [s], VG = 350 [s]). In vitro, phthalate-free materials exhibited higher dissolution in water after 14 days (VG = -260.78 ± 11.31 µg/mm2) compared to F (-76.12 ± 7.11 µg/mm2) and experienced faster hardening when stored in distilled water (F = 33.4 ± 0.30 Sh. A, VG = 59.2 ± 0.60 Sh. A). They also showed greater contractions. The connection of all materials to the prosthesis plate was consistent at 0.11 MPa. The highest counterbalance after 3 days was observed in TC = 3.53 ± 1.12%. Conclusions: Materials containing plasticizers that are not phthalates have worse mechanical properties than products containing these substances. Since phthalates are not allowed to be used indefinitely in medical devices, additional research is necessary, especially in vivo, to develop safe materials with superior functional properties to newer-generation alternatives. In vitro results often do not agree fully with those of in vivo outcomes.

The hard template method for the preparation of monodisperse mesoporous silica microspheres (MPSMs) has been established in recent years. In this process, in situ-generated silica nanoparticles (SNPs) enter the porous organic template and control the size and pore parameters of the final MPSMs. Here, the sizes of the deposited SNPs are determined by the hydrolysis and condensation rates of different alkoxysilanes in a base catalyzed sol-gel process. Thus, tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate (TEOS), tetrapropyl orthosilicate (TPOS) and tetrabutyl orthosilicate (TBOS) were sol-gel processed in the presence of amino-functionalized poly (glycidyl methacrylate-co-ethylene glycol dimethacrylate) (p(GMA-co-EDMA)) templates. The size of the final MPSMs covers a broad range of 0.5-7.3 µm and a median pore size distribution from 4.0 to 24.9 nm. Moreover, the specific surface area can be adjusted between 271 and 637 m2 g-1. Also, the properties and morphology of the MPSMs differ according to the SNPs. Furthermore, the combination of different alkoxysilanes allows the individual design of the morphology and pore parameters of the silica particles. Selected MPSMs were packed into columns and successfully applied as stationary phases in high-performance liquid chromatography (HPLC) in the separation of various water-soluble vitamins.

暂无摘要。

A new molecular rearrangement, the aza-Quasi-Favorskii rearrangement, has been developed for the construction of highly substituted aziridines. Electron-deficient O-sulfonyl oximes react readily with α,α-disubstituted acetophenone-derived enolates to furnish highly substituted aziridines via this unprecedented domino process. In-depth computational studies reveal an asynchronous yet concerted nitrenoid-type rearrangement pathway.

Generalized Modules for Membrane Antigens (GMMA) are outer membrane exosomes purified from Gram-negative bacteria genetically mutated to increase blebbing and reduce risk of reactogenicity. This is commonly achieved through modification of the lipid A portion of lipopolysaccharide. GMMA faithfully resemble the bacterial outer membrane surface, and therefore represent a powerful and flexible platform for vaccine development. Although GMMA-based vaccines have been demonstrated to induce a strong and functional antibody response in animals and humans maintaining an acceptable reactogenicity profile, the overall impact on immune cells and their mode of action are still poorly understood. To characterize the GMMA-induced immune response, we stimulated human peripheral blood mononuclear cells (hPBMCs) with GMMA from Shigella sonnei. We studied GMMA both with wild-type hexa-acylated lipid A and with the corresponding less reactogenic penta-acylated form. Using multicolor flow cytometry, we assessed the activation of immune cell subsets and we profiled intracellular cytokine production after GMMA stimulation. Moreover, we measured the secretion of thirty cytokines/chemokines in the cell culture supernatants. Our data indicated activation of monocytes, dendritic, NK, B, and γδ T cells. Comparison of the cytokine responses showed that, although the two GMMA have qualitatively similar profiles, GMMA with modified penta-acylated lipid A induced a lower production of pro-inflammatory cytokines/chemokines compared to GMMA with wild-type lipid A. Intracellular cytokine staining indicated monocytes and dendritic cells as the main source of the cytokines produced. Overall, these data provide new insights into the activation of key immune cells potentially targeted by GMMA-based vaccines.

Substituting natural products for traditional poison-killing antifouling agents is an efficient and promising method to alleviate the increasingly serious ecological crisis and aggravate the loss due to marine biofouling. Herein, the successful synthesis of poly(methyl methacrylate-co-ethyl acrylate-co-hexafluorobutyl methacrylate-co-isobornyl methacrylate) copolymer (PBAF) with borneol monomers and fluorine by a free radical polymerization method is reported. The PBA0.09F coating exhibits outstanding antibacterial and antifouling activity, achieving 98.2% and 92.3% resistance to Escherichia coli and Staphylococcus aureus, respectively, and the number of Halamphora sp. adhesion is only 26 (0.1645 mm2) in 24 h. This remarkable antibacterial and antifouling performance is attributed to the incorporation of fluorine components into the copolymer, which induces a low surface energy and hydrophobicity and the complex molecular structure of the natural nontoxic antifouling agent borneol. In addition, the results showed that the contents of the adhesion-related proteins mfp-3, mfp-5, and mfp-6 were significantly reduced, which proved that natural substances affect the secretion of biological proteins. Importantly, the PBAF coating exhibits excellent environmental friendliness and long-term stability. The antifouling mechanism is clarified, and an effective guide for an environmentally friendly antifouling coating design is proposed.

Clinically, adhesion failure is the most critical problem because of the failure of the optimal bond between denture base and the soft liner.
This study was performed to assess the tensile bond strength of two temporary soft liners to different denture base resins.
Forty-eight blocks with 16 samples each of heat-cured denture base resin of three different types were fabricated from custom-made stainless steel die after de-waxing mold space. Surface roughening of each acrylic resin specimens which bonds with soft liners was done by abrading the surface and to this temporary soft liners (Perma soft denture liner and Pro soft denture liner) were bonded. The universal testing machine was used to test the tensile strength of bonded space. The results were statistically analyzed using the Statistical Software IBM SPSS Statistics for Windows, version 20.0. (Armonk, NY, USA: IBM Corp.) using the Chi-square test, Post hoc Tukey\'s HSD, and two way ANOVA tests.
It was observed that Perma soft was prevalent over Pro-soft denture liner on the basis of tensile bond strength with all three different types of denture base resins. Trevalon HI and acrylic composite exhibited better bond strength results with both Perma soft and GC Pro-soft denture liner as compared to other types of denture base resins.
Perma soft had a better bond strength compared to Pro-soft denture liner in bonding modified denture base and conventional resins.
Résumé Fond: Cliniquement, l\'échec d\'adhésion est le problème le plus critique à cause de l\'échec de l\'obligation optimale entre la base de râtelier et le paquebot mou. Objectifs: Cette étude a été exécutée pour évaluer la force d\'obligation extensible de deux paquebots mous temporaires à de différentes résines de base de râtelier. Matériel et Méthodes: les blocs de Forty-eight avec 16 échantillons chacune de résine de base de râtelier heat-cured de trois différents types ont été fabriqués de l\'acier inoxydable custom-made meurent après que de-waxing moisissent l\'espace. Le fait de rendre rude de surface de chaques exemplaires de résine en acrylique que les obligations avec moules paquebots ont été faits en abrasant la surface et à ce temporaire les paquebots mous (Perma le paquebot de râtelier mol et le paquebot de râtelier mol Avantageux) étaient bonded. La machine de mise à l\'essai universelle a été utilisée pour évaluer la limite élastique à traction d\'espace bonded. Les résultats ont été statistiquement analysés en utilisant le Statistique Le logiciel IBM la Statistique de SPSS pour Windows, la version 20.0. (Armonk, NEW YORK, Etats-Unis: Société d\'IBM.) l\'utilisation de l\'épreuve de Chi-square, Postez le HSD de Tukey hoc, et deux voie. Résultats: Il a été remarqué que Perma mol était qui prévaut sur le paquebot de râtelier Pro-soft sur la base de l\'obligation extensible la force avec tous les trois différents types de râtelier base des résines. Trevalon SALUT et le composite en acrylique a exposé de meilleurs résultats de force d\'obligation avec tant Perma mous que GC Pro-soft le paquebot de râtelier en comparaison d\'autres types de râtelier basent des résines. Conclusion: Perma mol avait une meilleure obligation la force comparée au paquebot de râtelier Pro-soft dans bonding a modifié la base de râtelier et les résines conventionnelles.