The Design of Rapid Self-Healing Alginate Hydrogel with Dendritic Crosslinking Network.

Self-healing alginate hydrogels play important roles in the biological field due to their biocompatibility and ability to recover after cracking. One of the primary targets for researchers in this field is to increase the self-healing speed. Sodium alginate was oxidized, generating aldehyde groups on the chains, which were then crosslinked by poly(amino) amine (PAMAM) via Schiff base reaction. The dendritic structure was introduced to the alginate hydrogel in this work, which was supposed to promote intermolecular interactions and accelerate the self-healing process. Results showed that the hydrogel (ADA-PAMAM) formed a gel within 2.5 min with stable rheological properties. Within 25 min, the hydrogel recovered under room temperature. Furthermore, the aldehyde degree of alginate dialdehyde with a different oxidation degree was characterized through gel permeation chromatograph aligned with multi-angle laser light scattering and ultraviolet (UV) absorption. The chemical structure of the hydrogel was characterized through Fourier transform infrared spectroscopy and UV-vis spectra. The SEM and laser scanning confocal microscope (CLSM) presented the antibiotic ability of ADA-PAMAM against both S. aureus and E. coli when incubated with 10-7 CFU microorganism under room temperature for 2 h. This work presented a strategy to promote the self-healing of hydrogel through forming a dendritic dynamic crosslinking network.

A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy.

Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2 self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2 to O2 and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2 self-supplement composites provide a promising radiosensitizer for the radiotherapy field.

Proposed biosimilar pegfilgrastim (LA-EP2006) compared with reference pegfilgrastim in Asian patients with breast cancer: an exploratory comparison from two Phase III trials.

AIM: This is a pooled subgroup analysis of Asian patients enrolled in two Phase III confirmatory studies comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer. PATIENTS & METHODS: Women were randomized to LA-EP2006 (n = 90) or reference (n = 84) pegfilgrastim (Neulasta®, Amgen, Inc., CA, USA) for ≤6 cycles of TAC chemotherapy. Primary end point was duration of severe neutropenia during Cycle 1 (number of consecutive days with absolute neutrophil count <0.5 × 109/l) with equivalence confirmed if 95% CIs were within a ±1-day margin. RESULTS: Mean duration of severe neutropenia (days) in Cycle 1 was 1.36 ± 0.98 (LA-EP2006) versus 1.35 ± 1.06 (reference) (difference 0.01 days; 95% CI: -0.30-0.32, indicating equivalence). CONCLUSION: LA-EP2006 showed similar clinical efficacy and safety compared with reference pegfilgrastim.

Immobilization of polymeric g-C3N4 on structured ceramic foam for efficient visible light photocatalytic air purification with real indoor illumination.

The immobilization of a photocatalyst on a proper support is pivotal for practical environmental applications. In this work, graphitic carbon nitride (g-C3N4) as a rising visible light photocatalyst was first immobilized on structured Al2O3 ceramic foam by a novel in situ approach. Immobilized g-C3N4 was applied for photocatalytic removal of 600 ppb level NO in air under real indoor illumination of an energy-saving lamp. The photocatalytic activity of immobilized g-C3N4 was gradually improved as the pyrolysis temperature was increased from 450 to 600 °C. The optimized conditions for g-C3N4 immobilization on Al2O3 supports can be achieved at 600 °C for 2 h. The NO removal ratio could reach up to 77.1%, exceeding that of other types of well-known immobilized photocatalysts. Immobilized g-C3N4 was stable in activity and can be used repeatedly without deactivation. The immobilization of g-C3N4 on Al2O3 ceramic foam was found to be firm enough to overwhelm the continuous air flowing, which can be ascribed to the special chemical interaction between g-C3N4 and Al2O3. On the basis of the 5,5'-dimethyl-1-pirroline-N-oxide electron spin resonance (DMPO ESR) spin trapping and reaction intermediate monitoring, the active species produced from g-C3N4 under illumination were confirmed and the reaction mechanism of photocatalytic NO oxidation by g-C3N4 was revealed. The present work could provide new perspectives for promoting large-scale environmental applications of supported photocatalysts.

Preparation and evaluation of inhalable S-allylmercapto-N-acetylcysteine and nintedanib co-loaded liposomes for pulmonary fibrosis.

Orally marketed products nintedanib (NDNB) and pirfenidone (PFD) for pulmonary fibrosis (PF) are administered in high doses and have been shown to have serious toxic and side effects. NDNB can cause the elevation of galectin-3, which activates the NF-κB signaling pathway and causes the inflammatory response. S-allylmercapto-N-acetylcysteine (ASSNAC) can alleviate the inflammation response by inhibiting the TLR-4/NF-κB signaling pathway. Therefore, we designed and prepared inhalable ASSNAC and NDNB co-loaded liposomes for the treatment of pulmonary fibrosis. The yellow, spheroidal co-loaded liposomes with a particle size of 98.32±1.98 nm and zeta potential of -22.5 ± 1.58 mV were produced. The aerodynamic fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of NDNB were >50 % (81.14 %±0.22 %) and <5 µm (1.79 µm±0.06 µm) in the nebulized liposome solution, respectively. The results showed that inhalation improved the lung deposition and retention times of both drugs. DSPE-PEG 2000 in the liposome formulation enhanced the mucus permeability and reduced phagocytic efflux mediated by macrophages. ASSNAC reduced the mRNA over-expressions of TLR-4, MyD88 and NF-κB caused by NDNB, which could reduce the NDNB's side effects. The Masson's trichrome staining of lung tissues and the levels of CAT, TGF-ß1, HYP, collagen III and mRNA expressions of Collagen I, Collagen III and α-SMA in lung tissues revealed that NDNB/Lip inhalation was more beneficial to alleviate fibrosis than oral NDNB. Although the dose of NDNB/Lip was 30 times lower than that in the oral group, the inhaled NDNB/Lip group had better or comparable anti-fibrotic effects to those in the oral group. According to the expressions of Collagen I, Collagen III and α-SMA in vivo and in vitro, the combination of ASSNAC and NDNB was more effective than the single drugs for pulmonary fibrosis. Therefore, this study provided a new scheme for the treatment of pulmonary fibrosis.

Periplaneta americana extract promotes hard palate mucosal wound healing via the PI3K/AKT signaling pathway in male mice.

OBJECTIVES: This study aimed to investigate the effect of Periplaneta americana extract, a traditional Chinese medicine, on hard palate mucosal wound healing and explore the underlying mechanisms. DESIGN: Hard palate mucosal wound model was established and the effects of Periplaneta americana extract on hard palate mucosal wound healing were investigated by stereomicroscopy observation and histological evaluation in vivo. Human oral keratinocytes and human gingival fibroblasts, which play key roles in hard palate mucosal wound healing, were selected as the main research cells in vitro. The effects of Periplaneta americana extract on cell proliferation, migration, and collagen formation were determined by cell counting kit-8 (CCK-8) assay, Transwell assay, and Van Gieson staining. The underlying mechanism was revealed by RNA sequencing, and results were verified by western blot assay. RESULTS: Stereomicroscopy observation and H&E staining confirmed that Periplaneta americana extract accelerated the healing rate of hard palate mucosal wound (p < 0.001) in vivo. Transwell assay and Van Gieson staining assay showed that Periplaneta americana extract promoted the migration and collagen formation of human oral keratinocytes (p < 0.001) and human gingival fibroblasts (p < 0.001) in vitro. Mechanistically, RNA sequencing and western blot assay demonstrated that Periplaneta americana extract promoted hard palate mucosal wound healing via PI3K/AKT signaling, and the beneficial effects of Periplaneta americana extract were abrogated by the PI3K inhibitor LY294002. CONCLUSIONS: Periplaneta americana extract shows promising effects for the promotion of hard palate mucosal wound healing and may be a novel candidate for clinical translation.

Alpha-ketoglutarate promotes alveolar bone regeneration by modulating M2 macrophage polarization.

Objectives: Alpha-ketoglutarate (αKG) is an essential metabolite that plays a crucial role in skeletal homeostasis. Here we aim to investigate the effect of αKG on alveolar socket healing and reveal the underlying mechanism in the view of macrophage polarization. Methods: In a murine model pretreated with or without αKG, mandibular first molars were extracted. Mandibular tissues were harvested for microCT and histological analyses. Immunofluorescence was used to evaluate macrophage polarization during healing process. Macrophages with αKG/vehicle supplementation in vitro were proceeded to quantitative real-time PCR and flow cytometry to further elucidate the mechanism. Results: MicroCT and histological analyses showed accelerated healing and enhanced bone regeneration of extraction sockets in experimental group. αKG increased new bone volume in alveolar sockets and promoted the activity of both osteoblastogenesis and osteoclastogenesis. αKG administration reduced M1 pro-inflammatory macrophages in an early phase and promoted anti-inflammatory M2 macrophage polarization in a later phase. Consistently, the expressions of M2 marker genes were augmented in αKG group, while M1 marker genes were downregulated. Flow cytometry revealed the increased ratio of M2/M1 macrophages in cells treated with αKG. Conclusions: αKG accelerates the healing process of extraction sockets via orchestrating macrophage activation, with promising therapeutic potential in oral clinics.

Effect of polytetrafluoroethylene nanoplastics on combined inhibition of ciprofloxacin and bivalent copper on nitrogen removal, sludge activity and microbial community in sequencing batch reactor.

The work aimed to explore effects of polytetrafluoroethylene nanoplastics on joint inhibitions of ciprofloxacin and bivalent copper on the nitrogen removal in a sequencing batch reactor and its potential mechanisms. The addition of bivalent copper and/or ciprofloxacin reduced the ammonia nitrogen elimination rate with or without polytetrafluoroethylene nanoplastics. Adsorption kinetics and thermodynamics showed the binary bivalent copper and ciprofloxacin promoted their adsorptions by polytetrafluoroethylene nanoplastics. Polytetrafluoroethylene nanoplastics enhanced combined toxicities of ciprofloxacin and bivalent copper to sludge activities and microbial community involved into nitrification and denitrification due to the adsorption of ciprofloxacin and bivalent copper by polytetrafluoroethylene nanoplastics. With or without polytetrafluoroethylene nanoplastics, bivalent copper and/or ciprofloxacin caused more obvious level changes of protein than polysaccharide. This study provides novel insights for understanding the effect of combined heavy metals and antibiotics on the performance in a sequencing batch reactor with the nanoplastics stress.

Promotion of the osteogenic activity of an antibacterial polyaniline coating by electrical stimulation.

Electrical stimulation (ES) exhibits a positive role in promoting the cell activity of osteoblasts. Conducting polymers have the advantages of biocompatibility, good environmental stability and easy synthesis, which have been widely used as charge carriers for electrical stimulation; moreover, considering clinical applications, biomaterial-related infection is an important issue that needs to be solved. Thus, conducting polymers with both antibacterial and osteogenic properties are highly demanded for effect repair. However, it remains a challenge to combine these two characteristics efficiently in a simple way. Herein, an Ag-loaded poly(amide-amine) dendrimer was prepared by a simple chemical reduction procedure, which acted as a dopant for the polymerization of polyaniline (PANI) on biomedical titanium (Ti) sheets. The obtained PANI coating showed outstanding antibacterial properties against Gram-negative (E. coli) and Gram-positive (S. aureus) microbes with a 1000-fold increase when compared with that of pure Ti. In addition, note that the polymer coating together with ES facilitated the proliferation and differentiation of MC3T3. The alkaline phosphatase (ALP) activity and intracellular calcium content of the cells showed a 19.09% and 24.02% increase, respectively, when compared with the case of electrically stimulated Ti after 12 days. Moreover, the existence of PAMAM facilitated mineralization. The strategy developed herein is simple and can be easily manipulated, which shows potential applications in the coating of implants for hard tissue repair.

Surface phase separation, dewetting feature size, and crystal morphology in thin films of polystyrene/poly(ε-caprolactone) blend.

Thin films of polystyrene (PS)/poly(ε-caprolactone) (PCL) blends were prepared by spin-coating and characterized by tapping mode force microscopy (AFM). Effects of the relative concentration of PS in polymer solution on the surface phase separation and dewetting feature size of the blend films were systematically studied. Due to the coupling of phase separation, dewetting, and crystallization of the blend films with the evaporation of solvent during spin-coating, different size of PS islands decorated with various PCL crystal structures including spherulite-like, flat-on individual lamellae, and flat-on dendritic crystal were obtained in the blend films by changing the film composition. The average distance of PS islands was shown to increase with the relative concentration of PS in casting solution. For a given ratio of PS/PCL, the feature size of PS appeared to increase linearly with the square of PS concentration while the PCL concentration only determined the crystal morphology of the blend films with no influence on the upper PS domain features. This is explained in terms of vertical phase separation and spinodal dewetting of the PS rich layer from the underlying PCL rich layer, leading to the upper PS dewetting process and the underlying PCL crystalline process to be mutually independent.