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Journal of the American Chemical Society Nov 2023Polymeric spherulites are typically formed by melt crystallization: spherulitic growth in solution is rare and requires complex polymers and dilute solutions. Here, we...
Polymeric spherulites are typically formed by melt crystallization: spherulitic growth in solution is rare and requires complex polymers and dilute solutions. Here, we report the mild and unique formation of luminescent spherulites at room temperature via the simple molecule benzene-1,4-dithiol (BDT). Specifically, BDT polymerized into oligomers (PBDT) via disulfide bonds and assembled into uniform supramolecular nanoparticles in aqueous buffer; these nanoparticles were then dissolved back into PBDT in a good solvent (i.e., dimethylformamide) and underwent chain elongation to form spherulites (rPBDT) in 10 min. The spherulite geometry was modulated by changing the PBDT concentration and reaction time. Due to the step-growth polymerization and reorganization of PBDT, these spherulites not only exhibited robust structure but also showed broad clusterization-triggered emission. The biocompatibility and efficient cellular uptake of the spherulites further underscore their value as traceable drug carriers. This system provides a new pathway for designing versatile superstructures with value for hierarchical assembly of small molecules into a complicated biological system.
Topics: Crystallization; Polymers; Freezing; Nanoparticles
PubMed: 37921495
DOI: 10.1021/jacs.3c08356 -
Journal of Prosthodontics : Official... Dec 2023The mechanical and physical properties of implant screw access opening deteriorate if composite resin is not polymerized properly. Therefore, this study aimed to analyze...
PURPOSE
The mechanical and physical properties of implant screw access opening deteriorate if composite resin is not polymerized properly. Therefore, this study aimed to analyze the effect of using composite resin in implant access opening on the degree of conversion (DC).
MATERIALS AND METHODS
Two prosthetic materials (Co-Cr and zirconia), two types of composite resin (low and high viscosity), two light-cured resin depths (2 and 3 mm), and two polymerization methods (max-mode 10 s and mid-mode 20 s: 16 and 22 J/cm , respectively) were considered (n = 192). The DC of the polymerized composite resin was measured through Fourier-transform infrared spectroscopy. The top and bottom surfaces of the polymerized composite resin body were observed through scanning electron microscopy. Multiple linear regression analysis and analysis of variance were used to identify significant differences in DC (α = 0.05).
RESULTS
The DC was lower when the low-viscosity composite resin (β = -0.431), light-polymerized resin depth of 2 mm (β = -0.430), zirconia prosthesis (β = -0.191), and mid-mode polymerization method (β = -0.164) were used. The resin type, depth of resin to be light-cured, prosthesis material, and polymerization method had an effect on the DC.
CONCLUSIONS
Low-viscosity composite resin should be polymerized at a low irradiance and long polymerization time (such that the light-cured resin depth does not exceed 2 mm) to ensure proper composite resin polymerization in implant screw access opening.
Topics: Composite Resins; Polymerization; Materials Testing; Dental Implants; Spectroscopy, Fourier Transform Infrared; Surface Properties
PubMed: 36575827
DOI: 10.1111/jopr.13637 -
Journal of Immunology (Baltimore, Md. :... Aug 2023Cell spreading is an initial and critical step in neutrophil adhesion and migration, leading to neutrophil recruitment to inflammatory tissues. Sideroflexin (Sfxn)...
Cell spreading is an initial and critical step in neutrophil adhesion and migration, leading to neutrophil recruitment to inflammatory tissues. Sideroflexin (Sfxn) family proteins are metabolite transporters located in the mitochondrial membrane. Recombinant SFXN5 protein is a citrate transporter in vitro; however, whether Sfxn5 regulates any cellular behavior or function remains unknown. In this study, we found that small interfering RNA transfection or morpholino injection achieving Sfxn5 deficiency in neutrophils significantly decreased neutrophil recruitment in mice and zebrafish, respectively. Sfxn5 deficiency impaired neutrophil spreading and spreading-associated cellular phenotypes, such as cell adhesion, chemotaxis, and ROS production. Actin polymerization is critical for neutrophil spreading, and we found that actin polymerization in spreading neutrophils was partially inhibited by Sfxn5 deficiency. Mechanistically, we observed that the levels of cytosolic citrate and its downstream metabolic products, acetyl-CoA and cholesterol, were decreased in Sfxn5-deficient neutrophils. The levels of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a mediator for the regulation of actin polymerization by cholesterol, were reduced in the plasma membrane of Sfxn5-deficient neutrophils. Exogenous supplementation with citrate or cholesterol partially reversed the reduction in PI(4,5)P2 levels, defective neutrophil actin polymerization, and cell spreading. Altogether, we demonstrated that Sfxn5 maintains cytosolic citrate levels and ensures the synthesis of sufficient cholesterol to promote actin polymerization in a PI(4,5)P2-dependent manner during neutrophil spreading, which is essential for the eventual inflammatory recruitment of neutrophils. Our study revealed the importance of Sfxn5 in neutrophil spreading and migration, thus identifying, to our knowledge, for the first time, the physiological cellular functions of the Sfxn5 gene.
Topics: Animals; Mice; Actins; Neutrophils; Citric Acid; Zebrafish; Polymerization; Cholesterol
PubMed: 37326485
DOI: 10.4049/jimmunol.2200863 -
Advanced Science (Weinheim,... Aug 2023Gene therapy that employs therapeutic nucleic acids to modulate gene expression has shown great promise for diseases therapy, and its clinical application relies on the...
Gene therapy that employs therapeutic nucleic acids to modulate gene expression has shown great promise for diseases therapy, and its clinical application relies on the development of effective gene vector. Herein a novel gene delivery strategy by just using natural polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) as raw material is reported. EGCG first intercalates into nucleic acids to yield a complex, which then oxidizes and self-polymerizes to form tea polyphenols nanoparticles (TPNs) for effective nucleic acids encapsulation. This is a general method to load any types of nucleic acids with single or double strands and short or long sequences. Such TPNs-based vector achieves comparable gene loading capacity to commonly used cationic materials, but showing lower cytotoxicity. TPNs can effectively penetrate inside cells, escape from endo/lysosomes, and release nucleic acids in response to intracellular glutathione to exert biological functions. To demonstrate the in vivo application, an anti-caspase-3 small interfering ribonucleic acid is loaded into TPNs to treat concanavalin A-induced acute hepatitis, and excellent therapeutic efficacy is obtained in combination with the intrinsic activities of TPNs vector. This work provides a simple, versatile, and cost-effective gene delivery strategy. Given the biocompatibility and intrinsic biofunctions, this TPNs-based gene vector holds great potential to treat various diseases.
Topics: Polyphenols; Tea; Polymerization; Genetic Therapy; Nucleic Acids
PubMed: 37349886
DOI: 10.1002/advs.202302620 -
Acta Biomaterialia Nov 2023Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible...
Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates. STATEMENT OF SIGNIFICANCE: Biodegradable and biocompatible polymer-based biomaterials are recognized as potential future bioactive nanomedicines. To advance the development of such biomaterials, we developed polymerization platforms utilizing tailored chain transfer agents allowing the straightforward synthesis of hydrolytically degradable polymer biomaterials with tuned biodegradability from hours to several days. The platform allows for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterial serving as drug carriers or theranostics. The therapeutic potential was validated by preparation of polymer biomaterials containing pirarubicin, anticancer drug, bound via pH sensitive bond and by showing prolonged blood circulation and increased antitumor activity while keeping the drug side effects low. This work paves the way for future development of biodegradable polymer biomaterials with advanced properties in drug delivery.
Topics: Polymerization; Doxorubicin; Antineoplastic Agents; Drug Carriers; Polymers; Biocompatible Materials
PubMed: 37696413
DOI: 10.1016/j.actbio.2023.09.004 -
Food Research International (Ottawa,... Aug 2023The alginate oligosaccharides (AOS) possess versatile activities (such as antioxidant, anti-inflammatory, antitumor, and immune-regulatory activities) and have been the... (Review)
Review
The alginate oligosaccharides (AOS) possess versatile activities (such as antioxidant, anti-inflammatory, antitumor, and immune-regulatory activities) and have been the research topic in marine bioresource utilization fields. The degree of polymerization (DP) and the β-D-mannuronic acid (M)/α-L-guluronic acid (G)-units ratio strongly affect the functionality of AOS. Therefore, directed preparation of AOS with specific structures is essential for expanding the applications of alginate polysaccharides and has been the research topic in the marine bioresource field. Alginate lyases could efficiently degrade alginate and specifically produce AOS with specific structures. Therefore, enzymatic preparation of AOS with specific structures has drawn increasing attention. Herein, we systematically summarized the current research progress on the structure-function relation of AOS and focuses on the application of the enzymatic properties of alginate lyase to the specific preparation of various types of AOS. At the same time, current challenges and opportunities for AOS applications are presented to guide and improve the preparation and application of AOS in the future.
Topics: Alginates; Oligosaccharides; Structure-Activity Relationship; Antioxidants; Polymerization
PubMed: 37316063
DOI: 10.1016/j.foodres.2023.112990 -
Nature Communications Dec 2023Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into...
Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4 T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.
Topics: Actins; Polymerization; Cell Movement; Actin Cytoskeleton; Signal Transduction
PubMed: 38057317
DOI: 10.1038/s41467-023-43423-8 -
Operative Dentistry Jul 2023To fully maximize the potential of dual-polymerizing resin cements, a thorough understanding of how the light- and chemical-polymerizing components interact in a resin...
STATEMENT OF PROBLEM
To fully maximize the potential of dual-polymerizing resin cements, a thorough understanding of how the light- and chemical-polymerizing components interact in a resin system is required. Disorder in the polymerization process between the two components may hurt one of the components versus the other, affecting the overall properties and performance of the resin cements.
PURPOSE
Evaluate photo-polymerization delay time on dentin shear-bond strength and Vickers microhardness of dual-polymerizing resin cements.
METHODS AND MATERIALS
Shear bond strength (SBS) of self-adhesive (RelyX Unicem 2, 3M ESPE) and adhesive (RelyX Ultimate, 3M ESPE) dual-polymerizing resin cements were evaluated. Dentin specimens (n=80) were prepared for the SBS test according to ISO standard 29022:2013. Teeth were randomly allocated into eight groups based on the type of cement, and photo-polymerization delay times (0, 2, 5, and 10 minutes). Vickers microhardness test (HV) was performed following ASTM E384-17 (n=32) prepared based on cement type and photo-polymerization delay times; specimens were tested after 24 hours of storage. Statistical analysis was performed using two-way ANOVA to determine the individual and combined effects of resin cement type and photo-polymerization delay time on SBS and HV.
RESULTS
Resin cement and photo-polymerization delay times for the adhesive cement at 0- and 2-minute pairings had significantly higher SBS means than all other combinations (p<0.0001). Resin cement type was also statistically significant (p<0.0001). Resin cement type and photo-polymerization delay times were not significant (p=0.3550) for HV.
CONCLUSIONS
Photo-polymerization delay time affected dentin SBS with higher bond strength when photo-polymerization delay time was performed between 2 and 5 minutes with a self-adhesive resin cement, and between 0 and 2 minutes with an adhesive resin cement. Delaying photo-polymerization time to 10 minutes led to inferior dentin SBS and HV for both self-adhesive and adhesive dual-polymerizing resin cements.
Topics: Dental Bonding; Dental Cements; Dental Stress Analysis; Dentin; Glass Ionomer Cements; Materials Testing; Polymerization; Resin Cements
PubMed: 37352457
DOI: 10.2341/22-119-L -
Journal of Medicinal Chemistry Nov 2023Preclinical and clinical studies have demonstrated the synergistic effect of microtubule-targeting agents in combination with Janus kinase 2 (JAK2) inhibitors, prompting...
Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2.
Preclinical and clinical studies have demonstrated the synergistic effect of microtubule-targeting agents in combination with Janus kinase 2 (JAK2) inhibitors, prompting the development of single agents with enhanced therapeutic efficacy by dually inhibiting tubulin polymerization and JAK2. Herein, we designed and synthesized a series of substituted 2-amino[1,2,4]triazolopyrimidines and related heterocycles as dual inhibitors for tubulin polymerization and JAK2. Most of these compounds exhibited potent antiproliferative activity against the selected cancer cells, with compound being the most active. This compound effectively inhibits both tubulin assembly and JAK2 activity. Furthermore, phosphorylated compound (i.e., compound -) could efficiently convert to compound . Compound , whether it was administered directly or in the form of a phosphorylated prodrug (i.e., compound -), significantly inhibited the growth of A549 xenografts in nude mice. The present findings strongly suggest that compound represents a promising chemotherapeutic agent with high antitumor efficacy.
Topics: Animals; Mice; Humans; Tubulin; Structure-Activity Relationship; Tubulin Modulators; Cell Line, Tumor; Drug Screening Assays, Antitumor; Polymerization; Janus Kinase 2; Mice, Nude; Cell Proliferation; Antineoplastic Agents; Microtubules
PubMed: 37856840
DOI: 10.1021/acs.jmedchem.3c01690 -
Macromolecular Rapid Communications Dec 2023Polydiacetylenes, as a class of conjugated polymers with alternating conjugated C═C and C≡C bonds, have emerged as a promising probe material for biomedical Raman...
Polydiacetylenes, as a class of conjugated polymers with alternating conjugated C═C and C≡C bonds, have emerged as a promising probe material for biomedical Raman imaging, given their ultrastrong Raman scattering intensity. However, the relationship between the structure, especially the molecular length of polydiacetylenes, and their Raman scattering intensity remains unclear. In this work, a series of water-soluble polydiacetylenes, namely poly(deca-4,6-diynedioic acid) (PDDA) with different molecular weights (MWs), is prepared through controlled polymerization and degradation. The ultraviolet-visible (UV-vis) absorption spectroscopic and Raman spectroscopic studies on these polymers reveal that the Raman scattering intensity of PDDA increases nonlinearly with the MW. The MW-Raman scattering intensity relationship in the polymerization process is completely different from that in the degradation process. In contrast, the Raman scattering intensity increases more linearly with the maximal absorbance of the polymer, and the relationship between the Raman scattering intensity and the maximal absorbance of PDDA in the polymerization process is consistent with that in the degradation process. The Raman scattering intensity of PDDA hence exhibits a better dependence on the effective conjugation length of the polymer, which should guide the future design of conjugated polymers for Raman imaging applications.
Topics: Polymers; Spectrum Analysis, Raman; Polyacetylene Polymer; Molecular Weight
PubMed: 37713720
DOI: 10.1002/marc.202300412