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  • Hypoxia is the common characteristic of almost all solid tumors, which prevents therapeutic drugs from reaching the tumors. Therefore, the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned. As carbonic anhydrase IX (CA IX) is abundantly distributed on the hypoxia tumor cells, it is considered as a potential tumor biomarker. 4-(2-Aminoethyl)benzenesulfonamide (ABS) as a CA IX inhibitor has inherent inhibitory activity and good targeting effect. In this study, AgS quantum dots (QDs) were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe (AgS@polyethylene glycol (PEG)-ABS) through ligand exchange and amide condensation reaction. AgS@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II (NIR-II) fluorescence characteristics of AgS QDs. PEG modification of AgS QDs greatly improves its water solubility and stability, and therefore achieves high photothermal stability and high photothermal conversion efficiency (PCE) of 45.17%. Under laser irradiation, AgS@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells (CT-26) . It also has been proved that AgS@PEG-ABS can realize the effective treatment of hypoxia tumors and show good biocompatibility. Therefore, it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

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  • Extrusion printing based on biocompatible filaments offers a wide variety of targeted medical and dental applications in the area of personalized medicine, if combined with bioactive nanomaterials. However, this requires filament to be coated with bioactive nanomaterial. This study introduces a concept of a machine to coat filament with bioactive nanomaterials and its application. A machine was constructed with modules manufactured using additive manufacturing. A filament spool of polylactide (PLA) or glycol-modified polyethylene terephthalate (PETG) was transported through a copper tube, with the outer surface of the filament heated to the appropriate glass transition temperature to incorporate added nanomaterials such as nano-hydroxyapatite (nHA) or nano-fluorapatite(nFA). Coatings with nHA led to an increase in diameter of around 3 μm, while coatings with nFA increased the diameter by 4 μm. Printing of cubes with a standard extrusion printer platform using PLA or PETG filaments with added nHA or nFA has been successfully carried out. Scanning electron microscope (SEM) images of coated filaments and printed cubes showed an irregular distribution of nHA or nFA, which could be verified by energy dispersive X-ray analysis (EDX). Adding and adjusting bioactive nanomaterials to filament with a coating machine for filament proved to generate printable filaments. With the wide range of possible applications by different nanomaterials it is anticipated that extrusion printing can cover needs for personalized medicine and dentistry.

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  • Fatty acid profiles are crucial for the functionality and viability of lactobacilli used in food applications. Tween 80™, a common culture media additive, is known to influence bacterial growth and composition. This study investigated how Tween 80™ supplementation impacts the fatty acid profiles of six mesophilic lactobacilli strains ( spp., spp., ). Analysis of eleven strains revealed 29 distinct fatty acids. Tween 80™ supplementation significantly altered their fatty acid composition. Notably, there was a shift towards saturated fatty acids and changes within the unsaturated fatty acid profile. While some unsaturated fatty acids decreased, there was a concurrent rise in cyclic derivatives like lactobacillic acid (derived from vaccenic acid) and dihydrosterculic acid (derived from oleic acid). This suggests that despite the presence of Tween 80™ as an oleic acid source, lactobacilli prioritize the synthesis of these cyclic derivatives from precursor unsaturated fatty acids. Myristic acid and dihydrosterculic acid levels varied across strains. Interestingly, palmitic acid content increased, potentially reflecting enhanced incorporation of oleic acid from Tween 80™ into membranes. Conversely, cis-vaccenic acid levels consistently decreased across all strains. The observed fatty acid profiles differed from previous studies, likely due to a combination of factors including strain-specific variations and growth condition differences (media type, temperature, harvesting point). However, this study highlights the consistent impact of Tween 80™ on the fatty acid composition of lactobacilli, regardless of these variations. In conclusion, Tween 80™ significantly alters fatty acid profiles, influencing saturation levels and specific fatty acid proportions. This work reveals key factors, including stimulated synthesis of lactobacillic acid, competition for oleic acid incorporation, and strain-specific responses to myristic and dihydrosterculic acids. The consistent reduction in cis-vaccenic acid and the presence of cyclic derivatives warrant further investigation to elucidate their roles in response to Tween 80™ supplementation.

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  • Bioprinting is an automated bioassembly method that enables the formation of human tissue-like constructs to restore or replace damaged tissues. Regardless of the employed bioprinting method, cells undergo mechanical stress that can impact their survival and function postprinting. In this study, we investigate the use of a synthetic cell-like unit, giant unilamellar vesicles (GUVs), as adjuvants of the cellular function of human cells postprinting, or in future as the complete replacement of human cells. We analyzed the impact of two nozzle-based bioprinting methods (drop-on-demand and extrusion bioprinting) on the structure, stability, and function of GUVs. We showed that over 65% of the GUVs remain intact when printing at 0.5 bar, demonstrating the potential of using GUVs as a synthetic cell source. We further increased the stability of GUVs in a cell culture medium by introducing polyethylene glycol (PEG) into the GUV lipid membrane. The presence of PEG, however, diminished the structural properties of GUVs postprinting, and reduced the interaction of GUVs with human cells. Although the design of PEG-GUVs can still be modified in future studies for better cell-GUV interactions, we demonstrated that GUVs are functional postprinting. Chlorin e6-PEG-GUVs loaded with a fluorescent dye were bioprinted, and they released the dye postprinting only upon illumination. This is a new strategy to deliver carriers, such as growth factors, drugs, nutrients, or gases, inside large bioprinted specimens on a millimeter to centimeter scale. Overall, we showed that printed GUVs can augment the functionality of manufactured human tissues.

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  • Polylactic acid (PLA), a biodegradable polymer with low flexibility, is commonly plasticized with small molecules like tributyl citrate (TBC) for film production. However, these plasticizers, which lack chemical bonds or strong intermolecular interactions with the matrix, tend to migrate to the film surface over time. Their inclusion often compromises material strength for flexibility, increasing elongation at break but reducing tensile strength. In this research, by combining citric acid with n-butanol (B) and poly(ethylene glycol) diglycidyl ether (E), we synthesized three plasticizers, namely TE, TEB, and TEB, to enhance the flexibility of PLA. TEB and TEB are equipped with butyl ester groups that offer effective plasticizing effects. Additionally, the incorporation of long-chain alkyl featuring epoxy groups can boost the interaction with PLA. The results showed that the epoxy groups of the long-chain alkyl plasticizers can improve the elongation at break without compromising tensile strength significantly. The migration of plasticizer from PLA matrix can be reduced by strong interactions like chemical bonds, entanglements, and hydrogen bonding with PLA. TEB demonstrated the best plasticizing effect. Adding 15 portions of TE1B2 and TBC separately increased PLA's elongation at break to 304 % and 242 %, with tensile strengths of 36.1 MPa and 22.3 MPa, respectively.

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  • Generating stable and customizable topography on hydrogel surfaces with contact guidance potential is critical as it can direct/influence cell growth. This necessitates the development of new techniques for surface patterning of the hydrogels. We report on the design of a square grid template for surface patterning hydrogels. The template was 3-D printed and has the diameter of a well in a 24-well plate. Hyaluronic acid methacrylate (HA) hydrogel precursor solutions were cast on the 3D printed template's surface, which generated 3D square shape topographies on the HA hydrogel surface upon demolding. The 3D Laser Microscopy has shown the formation of a periodic array of 3D topographies on hydrogel surfaces. 3D Laser and Electron Microscopy Imaging have revealed that this new method has increased the surface area and exposed the underlying pore structure of the HA hydrogels. To demonstrate the method's versatility, we have successfully applied this technique to generate 3D topography on two more acrylate hydrogel formulations, gelatin Methacrylate and polyethylene glycol dimethacrylate. Human neonatal dermal fibroblast cells were used as a model cell line to evaluate the cell guidance potential of patterned HA hydrogel. Confocal fluorescence microscopy imaging has revealed that the 3D surface topographies on HA hydrogels can guide and align the actin filaments of the fibroblasts presumably due to the contact guidance mechanism. The newly developed methodology of 3D topography generation in acrylate hydrogels may influence the cell responses on hydrogel surfaces which can impact biomedical applications such as tissue engineering, wound healing, and disease modeling.

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  • Spatiotemporally controlled two-photon photodegradation of hydrogels has gained increasing attention for high-precision subtractive tissue engineering. However, conventional photolabile hydrogels often have poor efficiency upon two-photon excitation in the near-infrared (NIR) region and thus require high laser dosage that may compromise cell activity. As a result, high-speed two-photon hydrogel erosion in the presence of cells remains challenging. Here we introduce the design and synthesis of efficient coumarin-based photodegradable hydrogels to overcome these limitations. A set of photolabile coumarin-functionalized polyethylene glycol linkers are synthesized through a Passerini multicomponent reaction. After mixing these linkers with thiolated hyaluronic acid, semi-synthetic photodegradable hydrogels are formed in situ via Michael addition crosslinking. The efficiency of photodegradation in these hydrogels is significantly higher than that in nitrobenzyl counterparts upon two-photon irradiation at 780 nm. A complex microfluidic network mimicking the bone microarchitecture is successfully fabricated in preformed coumarin hydrogels at high speeds of up to 300 mm s and low laser dosage down to 10 mW. Further, we demonstrate fast two-photon printing of hollow microchannels inside a hydrogel to spatiotemporally direct cell migration in 3D. Collectively, these hydrogels may open new avenues for fast laser-guided tissue fabrication at high spatial resolution.

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  • Self-assembled materials capable of modulating their assembly properties in response to specific enzymes play a pivotal role in advancing 'intelligent' encapsulation platforms for biotechnological applications. Here, we introduce a previously unreported class of synthetic nanomaterials that programmatically interact with histone deacetylase (HDAC) as the triggering stimulus for disassembly. These nanomaterials consist of co-polypeptides comprising poly(acetyl L-lysine) and poly(ethylene glycol) blocks. Under neutral pH conditions, they self-assemble into particles. The hydrodynamic diameters of particles were typically withing the range of 108-190 nm, depending on degree of acetylation of the hydrophobic block. However, their stability is compromised upon exposure to HDACs, depending on enzyme concentration and exposure time. Our investigation, utilizing HDAC8 as the model enzyme, revealed that the primary mechanism behind disassembly involves a decrease in amphiphilicity within the block copolymer due to the deacetylation of lysine residues within the particles' hydrophobic domains. To elucidate the response mechanism, we encapsulated a fluorescent dye within these nanoparticles. Upon incubation with HDAC, the nanoparticle structure collapsed, leading to controlled release of the dye over time. Notably, this release was not triggered by denatured HDAC8, other proteolytic enzymes like trypsin, or the co-presence of HDAC8 and its inhibitor. We also demonstrated the biocompatibility and cellular effects of these materials in the context of drug delivery in different types of anticancer cell lines, such as MIA PaCa-2, PANC-1, cancer like stem cells (CSCs), and non-cancerous HPNE cells. We observed that the release of a model drug (such as a STAT3 pathway inhibitor, Napabucasin) can be loaded into these nanoparticles, with >90% of the dosage can be released over 3 h under the influence of HDAC8 enzyme in a controlled fashion. Further, we conducted a comprehensive computational study to unveil the possible interaction mechanism between enzymes and particles. By drawing parallels to the mechanism of naturally occurring histone proteins, this research represents a pioneering step toward developing functional materials capable of harnessing the activity of epigenetic enzymes such as HDACs.

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  • Clinical endocrinology has observed emerging endocrine complications following COVID-19 vaccination, amidst successful reductions in COVID-19 hospitalizations and deaths. The Pfizer-BioNTech and Moderna mRNA vaccines have demonstrated efficacy. Reports indicate a potential association between SARS-CoV-2 vaccination and diabetes, exploring interactions with ACE-2 receptors and molecular mimicry. Additionally, altered liver and kidney function tests post-vaccination prompt investigation into their role in predicting type 2 diabetes. This study aims to explore these biochemical abnormalities in a case-control, single-centre prospective study.

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  • An innovative pH-responsive nanocomposite, comprising agarose (AGA) modified with polyethylene glycol (PEG) hydrogel and coated with ferric oxide (FeO), has been formulated to facilitate the precise administration of 5-fluorouracil (5-Fu) to breast cancer cells. By utilizing a double emulsion technique, the size of the nanocomposites was significantly reduced through the application of almond oil; the inclusion of span 80 further improved their uniformity. The physiochemical properties of the nanocomposite were thoroughly examined by Fourier Transformed Infrared (FT-IR), X-ray diffraction (XRD), Field Emission-Scanning Electron Microscope (FE-SEM), Vibrating Sample Magnetometer (VSM), dynamic light scattering (DLS), and zeta potential tests. The verification of the uniform particle distribution was achieved by employing FE-SEM and VSM analyses. The average diameter of the particles was 223 nm, and their zeta potential was -47.6 mV. In addition, the nanocomposite exhibited a regulated release of 5-Fu at pH 5.4 and pH 7.4, as indicated by an in vitro drug release profile. PEG-AGA- FeO@5-Fu exhibited biocompatibility, as indicated by the lack of deleterious effects observed in tumor cells. This revolutionary nanocomposite demonstrates exceptional promise as a vehicle for breast cancer treatment, underscoring its significance as a significant progression in the ongoing pursuit of novel nanotechnologies for cancer therapy.

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