Developmental endothelial locus-1 promotes osteogenic differentiation and alveolar bone regeneration in experimental periodontitis with type 2 diabetes mellitus.

OBJECTIVES: This study sought to explore the role of developmental endothelial locus-1 (DEL-1) in osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and investigate the therapeutic effect of DEL-1 in ligature-induced experimental periodontitis with type 2 diabetes mellitus (T2DM). BACKGROUND: T2DM is a significant risk factor for periodontitis. Treatment modalities for periodontitis with T2DM are being explored. DEL-1 is a versatile protein that can modulate the different stages of inflammatory diseases including periodontitis. The direct effect of DEL-1 on osteogenic differentiation of PDLSCs in periodontitis with T2DM is poorly understood. METHODS: Primary hPDLSCs were isolated from periodontal ligament tissue and identified by flow cytometry. In osteogenesis experiments, alkaline phosphatase (ALP), Alizarin Red staining and western blot were used to assess the osteogenic effect of DEL-1 on hPDLSCs in high glucose and inflammation environments. The mouse model of ligature-induced experimental periodontitis was established. H&E and Masson's trichrome staining were used to assess the change of periodontal tissue after local periodontal injection of DEL-1. Immunohistochemical staining was used to evaluate osteogenic-related protein expression. RESULTS: hPDLSCs expressed mesenchymal stem cell (MSC)-specific surface markers and were negative for hematopoietic cell surface markers. hPDLSCs had the potential for multidirectional differentiation. DEL-1 could enhance the osteogenic differentiation of hPDLSCs in high glucose and inflammation environments, although it did not return to the control level. Histological staining showed that DEL-1 contributed to alveolar bone regeneration and osteogenic-related protein expression, but the degree of improvement in T2DM mice was lower than in non-T2DM mice. CONCLUSIONS: In summary, we demonstrated that DEL-1 could promote osteogenic differentiation of hPDLSCs in high glucose and inflammation environment and rescue alveolar bone loss in experimental periodontitis with T2DM, which could provide a novel therapeutic target for periodontitis with T2DM.

Anti-inflammatory cerium-containing nano-scaled mesoporous bioactive glass for promoting regenerative capability of dental pulp cells.

AIMS: This study aimed to investigate the anti-inflammatory and odontoblastic effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on dental pulp cells as novel pulp-capping agents. METHODOLOGY: Ce-MBGNs were synthesized using a post-impregnation strategy based on the antioxidant properties of Ce ions and proposed the first use of Ce-MBGNs for pulp-capping application. The biocompatibility of Ce-MBGNs was analysed using the CCK-8 assay and apoptosis detection. Additionally, the reactive oxygen species (ROS) scavenging ability of Ce-MBGNs was measured using the 2,7-Dichlorofuorescin Diacetate (DCFH-DA) probe. The anti-inflammatory effect of Ce-MBGNs on THP-1 cells was further investigated using flow cytometry and quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, the effect of Ce-MBGNs on the odontoblastic differentiation of the dental pulp cells (DPCs) was assessed by combined scratch assays, RT-qPCR, western blotting, immunocytochemistry, Alizarin Red S staining and tissue-nonspecific alkaline phosphatase staining. Analytically, the secretions of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Ce-MBGNs were confirmed to effectively scavenge ROS in THP-1-derived macrophages and DPCs. Flow cytometry and RT-qPCR assays revealed that Ce-MBGNs significantly inhibited the M1 polarization of macrophages (Mφ). Furthermore, the protein levels of TNF-α and IL-1ß were downregulated in THP-1-derived macrophages after stimulation with Ce-MBGNs. With a step-forward virtue of promoting the odontoblastic differentiation of DPCs, we further confirmed that Ce-MBGNs could regulate the formation of a conductive immune microenvironment with respect to tissue repair in DPCs, which was mediated by macrophages. CONCLUSIONS: Ce-MBGNs protected cells from self-produced oxidative damage and exhibited excellent immunomodulatory and odontoblastic differentiation effects on DPCs. As a pulp-capping agent, this novel biomaterial can exert anti-inflammatory effects and promote restorative dentine regeneration in clinical treatment. We believe that this study will stimulate further correlative research on the development of advanced pulp-capping agents.

Redox-Responsive Polymer Nanoreactors Based on Methionine Sulfoxide for Monitoring Cell Adhesion.

Expanding the category of redox-responsive monomers suitable for enzymolysis efficiency regulation and application to living biosystems is a prerequisite to complementing the fabrication of stimuli-responsive polymer nanoreactors. However, the development of redox-responsive monomers is severely limited by chemical oxidation and low biocompatibility. This work presents a protocol for overcoming this problem by the self-assembly of redox-responsive polymer nanoreactors containing segments of water-soluble methionine sulfoxide residues and poly(styrene-co-maleic anhydride-l-methionine), and by immobilizing α-l-fucosidase into the nanoreactors. These nanoreactors demonstrate highly selective responses to a mild redox triggered by H2O2 from the initial state (VO) to an oxidation state (VO1), and are reduced by methionine sulfoxide reductase A to mold the VO' state. It resulted in significantly enhanced enzymolysis efficiency and maximal reaction rates 8.1-fold (VO) and 23.3-fold (VO1) higher than those of the free enzyme. Moreover, cell adhesion was evaluated by the highly selective determination of l-fucose on cell surfaces. Using a combination of chemical oxidation and enzymatic reduction, this work achieves reiterative enzymolysis efficiency regulation of polymer nanoreactors, which has great potential for the construction of redox-responsive nanoreactors and for monitoring cell adhesion.

Poly(N,N-dimethylacrylamide)-stabilized gold nanoparticles as nanozymes with enhancement of catalytic activity for detection of lomefloxacin.

Recently, polymer-protected gold nanoparticles (AuNPs) have attracted extensive attention due to their good catalytic activities. However, how to regulate their catalytic activities by changing the polymer chain morphologies or the interactions between the ligands and the analytes through external stimuli is still a great challenge. This study describes a simple synthesis of AuNPs capped by thermo-responsive poly(N,N-dimethylacrylamide) (PDMAM). In comparison with three kinds of PDMAMs@AuNPs, PDMAM-2@AuNPs exhibited better peroxidase-mimic ability via the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with hydrogen peroxide (H2O2) to generate oxidized TMB (oxTMB). Interestingly, its catalytic activity could be regulated by changing environmental temperature. Importantly, the addition of the antibiotic lomefloxacin endowed the PDMAM-2@AuNPs with enhancement in catalytic efficiency due to electrostatic interactions and the increased levels of reactive oxygen species. Based on this principle, a protocol for highly selective and sensitive monitoring of lomefloxacin has been constructed with the color change from pale blue to deep blue. The ultraviolet-visible absorbance of oxTMB at the wavelength of 650 nm showed a good linear relationship with antibiotic concentration in the range of 0.25-10.0 µM (R2 = 0.990). The limit of detection was 0.1 µM. The practical application of the proposed protocol with the promoted peroxidase-mimic activity for the measurement of lomefloxacin in capsules was realized.

Array atomic force microscopy for real-time multiparametric analysis.

Nanoscale multipoint structure-function analysis is essential for deciphering the complexity of multiscale biological and physical systems. Atomic force microscopy (AFM) allows nanoscale structure-function imaging in various operating environments and can be integrated seamlessly with disparate probe-based sensing and manipulation technologies. Conventional AFMs only permit sequential single-point analysis; widespread adoption of array AFMs for simultaneous multipoint study is challenging owing to the intrinsic limitations of existing technological approaches. Here, we describe a prototype dispersive optics-based array AFM capable of simultaneously monitoring multiple probe-sample interactions. A single supercontinuum laser beam is utilized to spatially and spectrally map multiple cantilevers, to isolate and record beam deflection from individual cantilevers using distinct wavelength selection. This design provides a remarkably simplified yet effective solution to overcome the optical cross-talk while maintaining subnanometer sensitivity and compatibility with probe-based sensors. We demonstrate the versatility and robustness of our system on parallel multiparametric imaging at multiscale levels ranging from surface morphology to hydrophobicity and electric potential mapping in both air and liquid, mechanical wave propagation in polymeric films, and the dynamics of living cells. This multiparametric, multiscale approach provides opportunities for studying the emergent properties of atomic-scale mechanical and physicochemical interactions in a wide range of physical and biological networks.

Platinum-Gold Alloy Catalyzes the Aerobic Oxidation of Formic Acid for Hydrogen Peroxide Synthesis.

On-site hydrogen peroxide production through electrocatalytic and photocatalytic oxygen reduction reactions has recently attracted broad research interest. However, practical applications have thus far been plagued by the low activity and the requirement of complex equipment. Here, inspired by the process of biological hydrogen peroxide synthesis catalyzed by enzymes, we report a Pt-Au alloy to mimic the catalytic function of natural formate oxidase for hydrogen peroxide synthesis through aerobic oxidation of formic acid. The mass activity of the Pt-Au alloy is three times higher than that of formate oxidase. Density functional theory calculations revealed that the efficient dehydrogenation of formic acid and the high selectivity of the subsequent reduction of oxygen to hydrogen peroxide account for the high hydrogen peroxide productivity. In addition, the formic acid aqueous solution provides an acidic environment, which is conducive to the utilization of the in situ generated hydrogen peroxide for oxidation reactions, including C-H bond oxidation and sterilization.

Polyethylene liner cementation into a well-fixed metal acetabular shell for the management of periacetabular osteolysis: a systematic review.

PURPOSE: Although various papers have reported on the clinical performance of cup retention with cementation of a new liner and bone grafting in the management of well-fixed cups with polyethylene wear and periacetabular osteolysis after total hip arthroplasty (THA), no systematic review of this topic has been published to date. METHODS: Medline, EMBASE and Cochrane Library were searched for articles published from January 1999 to January 2019 using "osteolysis" AND "well-fixed", "osteolysis" AND "retro-acetabular", "bone graft" AND ("retention" OR "retained" OR "stable") AND "cup", and "cemented liner" AND "well-fixed". RESULTS: Nine articles were selected for review (186 cases, 76.1 months mean follow-up). The overall revision rate was 11.3% (21 hips) most commonly due to aseptic loosening (9/186 hips), dislocation (8/186 hips), and liner wear progression (2/186 cases). The reported square size of osteolytic lesions ranged from a mean of 465.84 mm2 to a max of 4,770 mm2. Almost all reported lesions treated with bone grafts resolved or did not progress 97% (72/74). All studies indicated improved pain and functional scores at follow-up. CONCLUSION: Cementation of a new liner with periacetabular bone grafting provides an alternative option to isolated liner exchange and cup revision for the management of periacetabular osteolysis in well-fixed cups with a disrupted locking mechanism or unavailable exchange liner. Further higher quality studies are required in order to examine if the use of highly cross-linked polyethylene, highly porous-coated cups, hydroxyapatite-coated cups, and small-diameter cups influence the clinical outcome of liner cementation in well-fixed cups with periacetabular osteolysis.

Impact of transparent tray-based application of bioactive glasses desensitizer on the permeability of enamel and dentin to hydrogen peroxide: an in vitro study.

BACKGROUND: To investigate the effect of transparent tray-based application of bioactive glasses (BGs) desensitizer on the permeability of enamel and dentin to hydrogen peroxide (H2O2). METHODS: Freshly extracted human first premolars were divided into 6 groups (n = 8). Group A and B: without pretreatments; Group C and E: treated with BGs desensitizer only; Group D and F: treated with BGs desensitizer dispensed with a transparent tray. After roots and pulp tissues of the treated tooth specimens were thoroughly removed, acetate buffer was added into pulp chambers and the treated specimens were immersed in distilled water (Groups A, E, and F) or 30% H2O2 (Groups B, C, and D) for 30 min at 37 °C. The amount of H2O2 in the pulp chamber of each group was measured using ultraviolet-visible spectrophotometry. RESULTS: In control groups (Group A, E, and F), H2O2 was not detected. The amount of pulpal H2O2 in Group B, C, and D were 21.149 ± 0.489 µg, 9.813 ± 0.426 µg, and 4.065 ± 0.268 µg respectively. One-way ANOVA analysis indicated that significant differences existed in these groups (F = 459.748, p < 0.05). CONCLUSIONS: The effect of BGs desensitizer in reducing the permeability of enamel and dentin to H2O2 could be enhanced when dispensed with a transparent tray.

Skeletal development of the chondrocranium in the tongue sole Cynoglossus semilaevis (Pleuronectiformes: Cynoglossidae).

This study provides a comprehensive description of chondrocranial development before, during and after larval metamorphosis in the tongue sole Cynoglossus semilaevis, a commercially valuable flatfish in China. Samples were collected at regular intervals ranging from 1 to 23 days post hatching (dph). Based on observations of cleared and double-stained specimens and images from sections stained with safranin O-fast green, major morphological events during early development were described. No cartilaginous structure was visible at hatching. From 2 dph onwards, cartilaginous structures such as the trabecular bar and some elements of the mandibular, hyoid and branchial arches appeared. At this time also, cartilaginous structures of the neurocranium started to form. Hypertrophic chondrocytes could be observed in many splanchnocranium elements at 5 dph. The start of ossification was indicated by alizarin red stain visible at 14 dph. At 17 dph, most of the cartilaginous skeleton was ossified. Soon after, the right eye started to migrate and pass through a slit beneath the dorsal-fin base and above the skull. Metamorphosis was complete at 20 dph, at which time the dorsal-fin base cartilage extended onto the anterior region of the head. Meanwhile, extremities of the hyoid and branchial arch elements remained cartilaginous. At 23 dph, endochondral ossification of the splanchnocranium was nearly complete. Unlike previous observations of other Pleuronectiformes, our study indicates that endochondral ossification of C. semilaevis skull cartilage occurs before metamorphosis.

An in vitro study evaluating the effect of ferrule design on the fracture resistance of endodontically treated mandibular premolars after simulated crown lengthening or forced eruption methods.

BACKGROUND: The purpose of this study was to evaluate the effect of ferrule design on the fracture resistance of endodontically treated mandibular first premolars after simulated crown lengthening and orthodontic forced eruption methods restored with a fiber post-and-core system. METHODS: Forty extracted and endodontically treated mandibular first premolars were decoronated to create lingual-to-buccal oblique residual root models, with a 2.0 mm height of the lingual dentine wall coronal to the cemento-enamel junction, and the height of buccal surface at the cemento-enamel junction. The roots were divided randomly into five equal groups. The control group had undergone incomplete ferrule preparation in the cervical root, with 0.0 mm buccal and 2.0 mm lingual ferrule lengths (Group F0). Simulated surgical crown lengthening method provided ferrule preparation of 1.0 mm (Group CL/F1) and 2.0 mm (Group CL/F2) on the buccal surface, with ferrule lengths of 3.0 mm and 4.0 mm on the lingual surface, respectively. Simulated orthodontic forced eruption method provided ferrule preparation of 1.0 mm (Group OE/F1) and 2.0 mm (Group OE/F2) on the buccal surface and ferrule lengths of 3.0 mm and 4.0 mm on the lingual surface, respectively. After restoration with a glass fiber post-and-core system and a cast Co-Cr alloy crown, each specimen was embedded in an acrylic resin block to a height on the root 2.0 mm from the apical surface of the crown margin and loaded to fracture at a 135° angle to its long axis in a universal testing machine. Data were analyzed statistically using two-way ANOVA with Tukey HSD tests and Fisher's test, with α = 0.05. RESULTS: Mean fracture loads (kN) for groups F0, CL/F1, CL/F2, OE/F1 and OE/F2 were as follows: 1.01 (S.D. = 0.26), 0.91 (0.29), 0.73 (0.19), 0.96 (0.25) and 0.76 (0.20), respectively. Two-way ANOVA revealed significant differences for the effect of ferrule lengths (P = 0.012) but no differences for the effect of cervical treatment methods (P = 0.699). The teeth with no buccal ferrule preparation in control group F0 had the highest fracture resistance. In contrast, the mean fracture loads for group CL/F2 with a 2.0-mm buccal and 4.0-mm lingual ferrule created by simulated crown lengthening method were lowest (P = 0.036). CONCLUSIONS: Increased apically complete ferrule preparation resulted in decreased fracture resistance of endodontically treated mandibular first premolars, regardless of whether surgical crown lengthening or orthodontic forced eruption methods been used.

Cloning, expression profiling and promoter functional analysis of Bone morphogenetic protein 6 and 7 in tongue sole (Cynoglossus semilaevis).

Bone morphogenetic proteins (BMPs) play crucial roles in vertebrate developmental process and are associated with the mechanisms which drive early skeletal development. As a first approach to elucidating the role of BMPs in regulating fish bone formation and growth, we describe the cloning, expression profiling and promoter functional analysis of bmp6 and bmp7 in tongue sole (Cynoglossus semilaevis). The full length of bmp6 and bmp7 cDNA sequences is 1939 and 1836 bp, which encodes a protein of 428 and 427 amino acids, respectively. Tissue expression distribution of bmp6 and bmp7 was examined in 14 tissues of mature individuals by quantitative real-time PCR (qRT-PCR). The results revealed that bmp6 was predominantly expressed in the gonad, and bmp7 exhibited the highest expression level in the dorsal fin. Further comparison of bmp6 expression levels between female and male gonads showed that the expression in the ovary was significantly higher than in the testis. Moreover, bmp6 and bmp7 expression levels were detected at 15 sampling time points of early developmental stages (egg, larva, juvenile and fingerling stages). The highest expression level of bmp6 was observed in the egg stage (multi-cell and gastrula stage); while bmp7 exhibited the highest expression in the larva stage (1-4 days old). The high expression levels of BMP6 in the ovary as well as at early embryonic stages indicated that the maternally stored transcripts of bmp6 might play a role in early embryonic development. Whole-mount in situ hybridization showed that bmp6 and bmp7 exhibited similar spatial expression patterns. Both bmp6 and bmp7 signals were first detected in the head and anterior regions in newly hatched larvae, and then, the mRNAs appeared in the crown-like larval fin, jaw, operculum and fins (pectoral, dorsal, pelvic and anal) along with early development. Subsequently, we characterized the 5'-flanking regions of bmp6 and bmp7 by testing the promoter activity by luciferase reporter assays. Positive regulatory regions were, respectively, detected at the location of -272 to +28 and -740 to -396 in bmp6 and bmp7 gene. The predicted transcription factor binding sites (CREB, AP1 and methyl-CpG-binding protein) in the regions might participate in the transcriptional regulation of these two genes.

Enzyme Mimics: Advances and Applications.

Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti-biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications.

Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified nanoliposomes.

Probucol (PB), an antioxidant drug, is commonly used as a lipid concentration lowering drug to reduce blood plasma cholesterol levels in the clinic. However, the therapeutic effects of this drug are negatively impacted by its poor water solubility and low oral absorption efficiency. In this study, a PEGylated G5 PAMAM dendrimer (G5-PEG) modified nanoliposome was employed to increase water solubility, transepithelial transport, and oral absorption of PB. The uptake mechanism was explored in vitro in Caco-2 cells with the results suggesting that the absorption improvement of G5-PEG modified PB-liposome (PB-liposome/G5-PEG) was related to P-glycoprotein (P-gp) efflux pump but was independent of caveolae endocytosis pathways. Additionally, plasma lipid concentration lowering effects of PB-liposome/G5-PEG were evaluated in vivo in a LDLR-/- hyperlipidemia mouse model. Compared with saline treated group, treatment with PB-liposome/G5-PEG significantly inhibited the increase of plasma total cholesterol (TC) and triglyceride (TG) of mice induced by a high fat diet. Moreover, its lipid concentration lowering effects and plasma drug concentration were greater than PB alone or commercial PB tablets. Our results demonstrated that PB-liposome/G5-PEG significantly increased the oral absorption of PB and therefore significantly improved its pharmacodynamic effects.

A severe case of iatrogenic botulism associated with COVID-19 infection.

Background: The botulinum toxin is an extremely potent substance that impacts the nervous system. There has been a rise in cases of medical poisoning associated with it, particularly in the field of plastic and aesthetic procedures, in recent years. Case description: A 51-year-old woman underwent a facial wrinkle reduction procedure with an unauthorized injection of 100 U of botulinum toxin at an unlicensed medical facility six days prior to hospitalization. Over time, her toxicity symptoms intensified, impacting her respiratory muscles, and she did not receive antitoxin treatment. She was concurrently diagnosed with a COVID-19 infection during this period. Nonetheless, she experienced a full recovery 86 days after the injection. Conclusion: Currently, there is no effective antidote for botulism. Nevertheless, the timely administration of antitoxin can contribute to reducing the duration of the illness, alleviating symptoms, and preventing its recurrence. It is essential to recognize that individual responses may vary, and in this instance, the absence of antitoxin treatment did not significantly prolong the course of the disease. Accurate diagnosis of medical poisoning can be based on injection history and clinical symptoms. Early indications like fatigue and dry mouth warrant particular attention, emphasizing the importance of immediate medical intervention. To address emergencies, the Center for Disease Control (CDC) should maintain an accessible supply of antitoxin. Patients with severe poisoning should be hospitalized until their respiratory muscle strength is fully restored.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

Mechanistic and functional aspects of the interaction of AR-23 with mammalian cell membrane and improvement of branched polyethylenimine-mediated gene transfection.

BACKGROUND: Previous studies have suggested that reducing the positive charge of melittin could increase endosomal release activity and improve branched polyethylenimine (BPEI)-mediated transfection. AR-23 is a melittin-related peptide from Rana tagoi, which shows 81% sequence identity with melittin but has less positively-charged residues than melittin. The present study aimed to investigate the mechanistic and functional aspects of the interaction of AR-23 with mammalian cells and thus improve BPEI-mediated gene transfection. METHODS: AR23 and two AR-23 analogs (AR-20 without positively-charged residues and AR-26 with the same positively-charged residues as melittin) were analyzed. Circular dichroism (CD) spectrometry was used to analyze the secondary structures of the peptides. Peptide-induced depolarization of cell membrane, the membrane-lytic activity of the peptides, and their potency with respect to enhancing the cellular uptake of calcein were evaluated. The physicochemical characters of complexes were measured and the effect of the peptides on BPEI-mediated transfection was determined. RESULTS: The CD spectra results indicated that a positive charge in AR-23 played a crucial role in maintaining the α-helical conformation, whereas an extra positive charge could not increase α-helical formation. AR-23 displayed a similar depolarization ability to melittin. However, AR-23 showed a lower membrane lytic activity under physiological conditions and a higher lytic activity at endosomal pH than melittin and AR-26, which possess more positive charges. Compared to melittin and AR-26, AR-23, with a higher endosomal escaping activity, resulted in a higher enhancement of BPEI-mediated gene transfection, as well as the maintainance of a lower cytotoxicity. CONCLUSIONS: We suggest that AR-23 may be considered as a potential enhancer for improving the transfection efficiency of cationic polymers.

Fabrication of Dual-Stimuli-Responsive Polymer Vesicles for Regulation of Enzymolysis Efficiency in A Cascade Reaction.

Enzymatic cascade reactions in confined microenvironments play important roles in cellular chemical transformation. Controlling enzymatic efficiency and eliminating substrate interference in cascade reactions is of great significance. To this end, a vesicle composed of poly(styrene-maleic anhydride-N-isopropylacrylamide)(P(S-M-NIP)) and functionalized with 1,2-bis(10,12- tricosadiynoyl)-sn-glycero-3-phosphocholine (DC89 PC) was designed herein. Based on the thermo-sensitive property of P(S-M-NIP) and the photo-responsive property of DC89 PC, a serial of dual-stimuli-responsive nanoreactors was constructed via enzymes encapsulation to tune their enzymolysis efficiencies. A kinetics study of the glucose oxidase-encapsulated nanoreactor indicated that its enzymolysis velocity increased 2.1- and 1.6-fold under heating and the ultraviolet (UV)-light irradiation, respectively. Consequently, an enzymatic cascade reaction in the proposed enzyme reactor encapsulated with ß-galactosidase and glucose oxidase was investigated. The results revealed a 2.9-fold enhancement in enzymolysis efficiency by changing the ambient temperature under UV irradiation. The dual-stimuli-responsive polymer vesicles could also eliminate H2 O2 interference during the enzymatic cascade reaction. The vesicles demonstrated potential for switch-membrane-permeability, while, the confined microenvironment played a key role in regulating the reactions upon the temperature change and the presence of UV light. Our synthetic multi-organelle-like system provides a new way to mimic the control of cascade reaction catalytic processes by programming the "open/close" sates of the nanocapsules.

Enhanced removal of heavy metals by α-FeOOH incorporated carboxylated cellulose nanocrystal: synergistic effect and removal mechanism.

Simultaneous and highly efficient removal of heavy metal cations and oxyanions is significant for both water and soil remediation, but it remains a major challenge due to the complexity. In this work, a novel hybrid of α-FeOOH incorporated carboxylated cellulose nanocrystal (Fe/CNC) is synthesized via a hydrothermal process, which shows improved α-FeOOH dispersion and heavy metal removal capacity. In single adsorbate system, maximum adsorption capacities toward Pb(II), Cd(II), and As(V) by Fe/CNC reach 126.06, 53.07, and 15.80 mg g-1, respectively, and the Fe leaching is much lower than that of α-FeOOH. In binary and ternary adsorption systems, simultaneous removal of Pb(II), Cd(II), and As(V) is proved, and the competition and synergy coexist among heavy metals. FTIR and XPS spectra have revealed the synergistic removal mechanism: Pb(II) and Cd(II) are mainly removed by surface complexation with oxygen-containing functional groups on C-CNC and α-FeOOH, and precipitation on the surface of α-FeOOH, while ligand exchange with Fe-OH is responsible for As(V) removal. The soil incubation experiments show that exchangeable and carbonate-bound Pb, Cd, and As are transformed into more stable forms in contaminated soil containing Fe/CNC composites. This work provides a novel composite material for remediation of heavy metal-contaminated environments.

Constructing triple-network cellulose nanofiber hydrogels with excellent strength, toughness and conductivity for real-time monitoring of human movements.

In recent years, there has been a lot of interest in developing composite hydrogels with superior mechanical and conductive properties. In this study, triple-network (TN) cellulose nanofiber hydrogels were prepared by using cellulose nanofiber as the first network, isotropic poly(acrylamide-co-acrylic acid) as the second network, and polyvinyl alcohol as the third network via a cyclic freezing-thawing process. The strong (9.43 ± 0.14 MPa tensile strength, (445.5 ± 7.0)% elongation-at-break), tough (15.12 ± 0.14 MJ/m3 toughness), and conductive (0.0297 ± 0.00021 S/cm ionic conductivity) TN cellulose nanofiber hydrogels were effectively created after being pre-stretched in an external force field, cross-linked by Fe3+ and added Li+. The produced composite TN cellulose nanofiber hydrogels were successfully used as a flexible sensor for real-time monitoring and detecting human movements, highlighting their potential for wearable electronics, medical technology, and human-machine interaction. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Acrylamide (PubChem CID: 6579); Acrylic acid (PubChem CID: 6581); Ammonium persulfate (PubChem CID: 6579); N, N'-methylene bisacrylamide (PubChem CID: 17956053); Sodium bromide (PubChem CID: 253881); Sodium hydroxide (PubChem CID: 14798); Sodium hypochlorite (PubChem CID: 23665760); Sodium chlorite (PubChem CID: 23668197); 2,2,6,6-tetramethylpiperidinyl-1-oxide (PubChem CID: 2724126); Polyvinyl alcohol (PubChem CID: 11199); Lithium chloride (PubChem CID: 433294); Iron nitrate nonahydrate (PubChem CID: 129774236).

A novel lncRNA-mediated epigenetic regulatory mechanism in periodontitis.

Periodontitis is a highly prevalent chronic inflammatory disease with an exaggerated host immune response, resulting in periodontal tissue destruction and potential tooth loss. The long non-coding RNA, LncR-ANRIL, located on human chromosome 9p21, is recognized as a genetic risk factor for various conditions, including atherosclerosis, periodontitis, diabetes, and cancer. LncR-APDC is an ortholog of ANRIL located on mouse genome chr4. This study aims to comprehend the regulatory role of lncR-APDC in periodontitis progression. Our experimental findings, obtained from lncR-APDC gene knockout (KO) mice with induced experimental periodontitis (EP), revealed exacerbated bone loss and disrupted pro-inflammatory cytokine regulation. Downregulation of osteogenic differentiation occurred in bone marrow stem cells harvested from lncR-APDC-KO mice. Furthermore, single-cell RNA sequencing of periodontitis gingival tissue revealed alterations in the proportion and function of immune cells, including T and B cells, macrophages, and neutrophils, due to lncR-APDC silencing. Our findings also unveiled a previously unidentified epithelial cell subset that is distinctively presenting in the lncR-APDC-KO group. This epithelial subset, characterized by the positive expression of Krt8 and Krt18, engages in interactions with immune cells through a variety of ligand-receptor pairs. The expression of Tff2, now recognized for its role in chronic inflammatory conditions, exhibited a notable increase across various tissue and cell types in lncR-APDC deficient mice. Additionally, our investigation revealed the potential for a direct binding interaction between lncR-APDC and Tff2. Intra-gingival administration of AAV9-lncR-APDC was shown to have therapeutic effects in the EP model. In conclusion, our results suggest that lncR-APDC plays a critical role in the progression of periodontal disease and holds therapeutic potential for periodontitis. Furthermore, the presence of the distinctive epithelial subpopulation and significantly elevated Tff2 levels in the lncR-APDC-silenced EP model offer new perspectives on the epigenetic regulation of periodontitis pathogenesis.