Functionalization of Covalent Organic Frameworks with Peptides by Polymer-Assisted Surface Modification and the Application for Protein Detection.

Although covalent organic frameworks (COFs) have received extensive attention for biomedical research due to their unique properties, their application is still hindered by the challenges of incorporating COFs with functional biomolecules. Since peptides have shown advantages in biomedical applications, herein, we propose the functionalization of COFs with peptides by a polymer-assisted surface modification strategy. Furthermore, a method based on the peptide-functionalized COFs for protein detection has also been developed to demonstrate their application potential. With the help of the polymers, peptides and horseradish peroxidase are attached onto COFs with a high surface density, and the developed method has achieved simple and sensitive detection of the secreted protein acidic and rich in cysteine. We speculate that the facile method proposed in this work to prepare peptide-functionalized COFs can not only benefit protein detection but also promote more biomedical applications of COFs.

Immobilization of horseradish peroxidase on electrospun magnetic nanofibers for phenol removal.

In this study, Fe3O4/polyacrylonitrile (PAN) magnetic nanofibers (MNFs) were fabricated by electrospinning method to immobilize the horseradish peroxidase (HRP), making which a complex platform for phenol removal application. Results indicated that, the average diameter of MNFs was about 200-400 nm and the maximum saturation magnetic induction was 19.03 emu/g. Compared with the free HRP, the modified HRP showed no change in optimum pH, but showed higher catalytic activity. Moreover, HRP immobilized MNFs (H-MNFs) with 40% Fe3O4 nanoparticles loading had the lowest HRP loading, but had the highest relative activity, because of the magnetic synergy with the presence of MNPs. Subsequently, the 40% H-MNFs was used for the remediation of phenol wastewater, achieved the removal efficiency of phenol to 85% in the first round use, and remained 52% of efficiency after 5 recycles using. It was expected that the H-MNFs could be a potential application in wastewater treatment such as phenol removal.

Improving Plasma Stability and Bioavailability In Vivo of Gemcitabine Via Nanoparticles of mPEG-PLG-GEM Complexed with Calcium Phosphate.

PURPOSE: Despite being widely used for the treatment of several solid tumors, Gemcitabine (GEM) exhibits several suboptimal pharmacokinetic properties. Therefore, the design of nanoparticle delivery systems is a promising strategy to enhance GEM pharmacokinetic properties. METHODS: In this work, the polymeric material methoxy poly(ethylene glycol)-block-poly(L-glutamic acid)-graft-gemcitabine (mPEG-b-PLG-g-GEM) was synthesized through the covalent conjugation of GEM with the carboxylic group of methoxy poly(ethylene glycol)-block-poly (L-glutamic acid) (mPEG-b-PLG) (mPEG113, Mn = 5000). mPEG-PLG-GEM/CaP nanoparticles were prepared through the simple mixing of calcium and phosphate/mPEG-PLG-GEM solutions. mPEG-PLG-GEM was embedded in the calcium phophate (CaP) backbone via electrostatic interactions. RESULTS: After incubation in plasma at 37°C for 24 h, gemcitabine was degraded by 24.6% for the mPEG-PLG-GEM, 14.7% for the mPEG-PLG-GEM/CaP nanoparticles, and 90% for the free gemcitabine solution. It was observed that mPEG-PLG-GEM and mPEG-PLG-GEM/CaP improved the area-under-curve (AUC) values by 5.26-fold and 6.33-fold compared to free drug, respectively. CONCLUSION: The amide bond linked gemcitabine polymers was able to protect GEM from cytidine deaminase degradation in vivo, and the skeleton formed by the calcium phosphate enhanced the stability and prolonged the half-life of GEM. Importantly, mPEG-PLG-GEM/CaP nanoparticles elevated the GEM plasma concentration in an animal model.

Nifedipine di-matrix depot tablets prepared by compression coating for obtaining zero-order release.

Compression coating is a possible process for obtaining zero-order release. Nifedipine compression-coated (CC) di-matrix depot tablets were prepared from a single punch tablet press with low viscosity hydroxypropyl cellulose (HPC-L) as the inner polymer, and with middle viscosity hydroxypropyl cellulose (HPC-M), HPC-L and Eudragit RSPO as outer polymers. The release behavior and mechanisms in vitro of the final tablets were investigated, and gravimetric analysis was used to study the release mechanism. The fast release of the core depot and slow release of the outer depot with time formed total zero-order release. The results showed that the formulation presented ideal zero-order release at the weight ratio of nifedipine 3:5 (core: layer), the combination of HPC-L and HPC-M (56:25) in the outer depot, and with the core depot placed in the center. The CC tablets released to more than 95% in 24 h and fitted a zero-order model with the equation Mt/M∞ = 0.038t (R2 = 0.98555). In conclusion, zero-order release of nifedipine over 24 h could be achieved by applying polymer HPC-L and HPC-M with the compression coating technique.

Biomaterials and bioelectronics for self-powered neurostimulation.

Self-powered neurostimulation via biomaterials and bioelectronics innovation has emerged as a compelling approach to explore, repair, and modulate neural systems. This review examines the application of self-powered bioelectronics for electrical stimulation of both the central and peripheral nervous systems, as well as isolated neurons. Contemporary research has adeptly harnessed biomechanical and biochemical energy from the human body, through various mechanisms such as triboelectricity, piezoelectricity, magnetoelasticity, and biofuel cells, to power these advanced bioelectronics. Notably, these self-powered bioelectronics hold substantial potential for delivering neural stimulations that are customized for the treatment of neurological diseases, facilitation of neural regeneration, and the development of neuroprosthetics. Looking ahead, we expect that the ongoing advancements in biomaterials and bioelectronics will drive the field of self-powered neurostimulation toward the realization of more advanced, closed-loop therapeutic solutions, paving the way for personalized and adaptable neurostimulators in the coming decades.

Functionalized electrospun nanofibers to enhance ß-Galactosidase immobilization and catalytic activity for efficient galactooligosaccharide synthesis.

This study aimed to immobilize ß-galactosidase (ß-GAL) into enhanced polystyrene (PS) electrospun nanofiber membranes (ENMs) with functionalized graphene oxide (GO). Initially, GO sheets were functionalized by salinization with 3-aminopropyl triethoxysilane (APTES). Then the ENMs (PS, PS/GO, and PS/GO-APTES) were prepared and characterized. Then, the ß-GAL was immobilized in the different ENMs to produce the ß-GAL-bound nanocomposites (PS-GAL, PS/GO-GAL, and PS/GO-APTES-GAL). Immobilization of ß-GAL into PS/GO-APTES significantly improved enzyme adsorption by up to 87 %. Also, PS/GO-APTES-GAL improved the enzyme activity, where the highest enzyme activity was obtained at enzyme concentrations of 4 mg/L, 50 °C, and pH 4.5. Likewise, the storage stability and reusability of immobilized ß-GAL were improved. Furthermore, this process led to enhanced catalytic behavior and transgalactosylation efficiency, where GOS synthesis (72 %) and lactose conversion (81 %) increased significantly compared to the free enzyme. Overall, the immobilized ß-GAL produced in this study showed potential as an effective biocatalyst in the food industry.

Novel Lipase Reactor based on Discontinuous Interfaces in Hydrogel-Organogel Hybrid Gel: A Preliminary Exploration.

According to the "interfacial activation" mechanism, constructing a sufficient interface is the key strategy for lipase-catalytic system designing. Based on the "infinite interface in finite three-dimensional space" logic, in the current study, poly(N,N-dimethylacrylamide) (PDMA)-polybutyl methacrylate (PBMA) hybrid gels were prepared by a two-step crosslinking strategy, subsequently constructed as lipase-interfacial catalytic systems. The results confirm that the PDMA-PBMA hybrid gels with "networks in pores" structures could swell both the aqueous phase and organic phase. The balance between water swelling and isooctane swelling, hybrid gel space (height control), and the lipase entry manner significantly affect the interface construction and consequently the catalytic efficiency. The enzyme-substrate contact rate affected by swelling leads to three catalytic stages. Considering the spatial barrier and distribution of lipases, a potential high-performance lipase reactor can be assembled from small-size, lamellar-like, and porous hybrid gels. The reactors also show good time storage and low temperature tolerance.

Disrupted microbiota-barrier-immune interaction in phthalates-mediated barrier defect in the duodenum.

As one of the most used phthalates, Di (2-ethylhexyl) phthalate (DEHP) is a widespread environmental contaminant. Extremely persistent plastic can enter the food chain of animals through the aquatic environment, affect metabolic pathways and cause damage to the digestive system. But the molecular mechanism of its toxic effects on the duodenum in birds has not been elucidated. To investigate the toxicity of phthalates in the duodenum, quails were gavaged with 250, 500, and 750 mg/kg doses of DEHP for 45 days, and water and oil control groups were retained. This study revealed that subchronic exposure to DEHP could lead to duodenal barrier defect in quail. The damage to duodenum was reflected in a reduction in V/C and tight junction proteins. Moreover, DEHP also led to a breakdown of antimicrobial defenses through the flora derangement, which acted as a biological barrier. The massive presence of Lipopolysaccharide (LPS) led to the activation of TLR4 receptors. In addition, DEHP activated oxidative stress, which synergized the inflammatory response induced by the TLR4-NFκB pathway, and further promoted duodenum damage. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction.

Gap Junction Protein Connexin 43 as a Target Is Internalized in Astrocyte Neurotoxicity Caused by Di-(2-ethylhexyl) Phthalate.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in plastic products, consumer products, and packaging materials. It is of great health concern in both animals and humans as it released into the environment and entered into the body from plastic products over time, thereby resulting in neurotoxicity. As a pivotal regulator of the central nervous system (CNS), astrocytes, are crucial for maintaining brain homeostasis. Nevertheless, the underlying reason for astrocyte neurotoxicity due to DEHP exposure remains incompletely understood. Here, using an in vivo model of neurotoxicity in quail, this study summarizes that Cx43 is internalized by phosphorylation and translocated to the nucleus as a consequence of DEHP exposure in astrocytes. This study further demonstrated that astrocytes transformed to pro-inflammatory status and induced the formation of autophagosomes. Of note, integrated immunofluorescent codetection approaches revealed an overexpression of the glial fibrillary acidic protein (GFAP) and down-expression of Cx43 in astrocytes. Therefore, in terms of neurotoxicity, this experiment in vivo models directly linked Cx43 internalization to autophagy and neuroinflammation and ultimately locked these changes to the astrocytes of the brain. These findings unveil a potential approach targeting Cx43 internalization for the treatment of neurodegeneration caused by DEHP exposure in astrocytes.

Fabrication of an Aptamer-Coated Liposome Complex for the Detection and Profiling of Exosomes Based on Terminal Deoxynucleotidyl Transferase-Mediated Signal Amplification.

The exosome is a promising biomarker carrying many kinds of membrane proteins with huge heterogeneity, so the sensitive and multiplex analysis of exosomes is very significant for disease diagnosis and exploration of their biological functions. Herein, we propose an efficient method for highly sensitive detection and heterogeneity identification of exosomes based on the design and fabrication of an aptamer-coated liposome complex coupled with terminal deoxynucleotidyl transferase (TdT)-mediated polymerization. Specifically, in the presence of target exosomes, the aptamers immobilized on the surface of 1,2-dioleoyl-3-trimethylammonium-propane liposomes prefer to bind with exosomal membrane proteins due to the high affinity. The resulting aptamer-exosome complex will be accessible to TdT to switch on the polymerization reaction for signal amplification, achieving highly sensitive detection of exosomes. Furthermore, the proposed method can be employed to profile different exosomal membrane proteins by making use of a cluster of corresponding aptamers and obtain a fingerprint map of various cancer cell-derived exosomes. Thus, our approach may provide a highly sensitive and robust strategy for the identification of exosome heterogeneity with advantages of being label-free and having no separation, potentially enabling the precise subpopulation of exosomes with practical value in clinical applications.