Peptide functionalized biomimetic gene complexes enhance specificity for vascular endothelial regeneration.

Gene delivery presents great potential in endothelium regeneration and prevention of vascular diseases, but its outcome is inevitably limited by high shear stress and instable microenvironment. Highly efficient nanosystems may alleviate the problem with strong dual-specificity for diseased site and targeted cells. Hence, biomimetic coatings incorporating EC-targeting peptides were constructed by platelets and endothelial cells (ECs) for surface modification. A series of biomimetic gene complexes were fabricated by the biomimetic coatings to deliver pcDNA3.1-VEGF165 plasmid (pVEGF) for rapid recovery of endothelium. The gene complexes possessed good biocompatibility with macrophages, stability with serum and showed no evident cytotoxicity for ECs even at very high concentrations. Furthermore, the peptide modified gene complexes achieved selective internalization in ECs and significant accumulation in endothelium-injured site, especially the REDV-modified and EC-derived gene complexes. They substantially enhanced VEGF expression at mRNA and protein levels, thereby enabling a wound to heal completely within 24 h according to wound healing assay. In an artery endothelium-injured mouse model, the REDV-modified and EC-derived gene complexes presented efficient re-endothelialization with the help of enhanced specificity. The biomimetic gene complexes offer an efficient dual-targeting strategy for rapid recovery of endothelium, and hold potential in vascular tissue regeneration.

Strontium doped Fe-based porous carbon for highly efficient electrocatalytic ORR and MOR reactions.

The catalytic activity improvement of Fe-based active sites derived from metal organic frameworks toward oxygen reduction reaction (ORR) and methanol oxidation reaction (MOR) remains a major challenge. In this study, the growth of strontium decorated 2-methylimidazole zinc salt (Sr/ZIF-8) is prepared as a carrier to vapor deposited iron formation Sr doped Fe-based nitrogen-doped carbon framework (named as Sr/FeNC). After high-temperature pyrolysis and vapor deposition, strontium carbonate nanocrystals are evenly dispersed on the shrunk dodecahedron carbon frame and multitudinous Fe-based active catalytic sites are embedded in carbon skeleton. The optimal Sr/FeNC-2 catalyst demonstrates the outstanding ORR performance in terms of a half-wave potential of 0.851 V and an onset potential of 0.90 V, while Sr/FeNC-2 exhibits a high current density of 18.2 mA cm-2 and a lower Tafel slope of 21 mV dec-1 in MOR. The exceptional catalytic activity could be ascribed to the synergistic coupling effect of strontium compounds with Fe-based catalytic sites (Fe-Nx, Fe, and iron oxide). In particular, the formation of SrCO3 affects the bonding configuration of the iron species sites, leading to an optimization of the electronic structure within the multihole carbon matrix. The synthetic approach presents a prospective strategy for future endeavors in developing innovative and advanced bifunctional catalysts for ORR and MOR.

Glycyrrhetinic Acid Mitigates Radiation-Induced Pulmonary Fibrosis via Inhibiting the Secretion of TGF-ß1 by Treg Cells.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a common side effect of radiation therapy for thoracic tumors without effective prevention and treatment methods at present. The aim of this study was to explore whether glycyrrhetinic acid (GA) has a protective effect on RIPF and the underlying mechanism. METHODS AND MATERIALS: A RIPF mouse model administered GA was used to determine the effect of GA on RIPF. The cocultivation of regulatory T (Treg) cells with mouse lung epithelial-12 cells or mouse embryonic fibroblasts and intervention with GA or transforming growth factor-ß1 (TGF-ß1) inhibitor to block TGF-ß1 was conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-ß1 levels was performed to verify the roles of TGF-ß1 and Treg cells. RESULTS: GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltration, TGF-ß1 levels, epithelial mesenchymal transition (EMT), and myofibroblast (MFB) transformation in mice after irradiation. Treg cell-induced EMT and MFB transformation in vitro were prevented by GA, as well as a TGF-ß1 inhibitor, by decreasing TGF-ß1. Furthermore, reinfusion of Treg cells upregulated TGF-ß1 levels and exacerbated RIPF in GA-treated RIPF mice. CONCLUSIONS: GA can improve RIPF in mice, and the corresponding mechanisms may be related to the inhibition of TGF-ß1 secreted by Treg cells to induce EMT and MFB transformation. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF.

MiR-223-3p attenuates radiation-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages.

Macrophage pyroptosis plays an important role in the development of radiation-induced cell and tissue damage, leading to acute lung injury. However, the underlying mechanisms of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)-mediated macrophage pyroptosis and the regulatory factors involved in radiation-induced pyroptosis are unclear. In this study, the expression of the NLRP3 inflammasome and pyroptosis-associated factors in murine macrophage cell lines was investigated after ionizing radiation. High-throughput RNA sequencing was performed to identify and characterize miRNAs and mRNA transcripts associated with NLRP3-mediated cell death. Our results demonstrated that cleaved-caspase-1 (p10) and N-terminal domain of gasdermin-D (GSDMD-N) were upregulated, and the number of NLRP3 inflammasomes and pyroptotic cells increased in murine macrophage cell lines after irradiation (8 Gy). Comparativeprofiling of 300miRNAs revealed that 41 miRNAsexhibited significantly different expression after 8 Gy of irradiation. Granulocyte-specific microRNA-223-3p (miR-223-3p) is a negative regulator of NLRP3. In vitro experiments revealed that the expression of miR-223-3p was significantly altered by irradiation. Moreover, miR-223-3p decreased the expression of NLRP3 and proinflammatory factors, resulting in reduced pyroptosis in irradiated murine macrophages. Subsequently, in vivo experiments revealed the efficacy of miR-223-3p supplementation in ameliorating alveolar macrophage (AM) pyroptosis, attenuating the infiltration of inflammatory monocytes, and significantly alleviating the severity of acute radiation-induced lung injury (ARILI). Our findings suggest that the miR-223-3p/NLRP3/caspase-1 axis is involved in radiation-induced AM pyroptosis and ARILI.

Prognostic Value of Serum Transferrin Level before Radiotherapy on Radio-Sensitivity and Survival in Patients with Nasopharyngeal Carcinoma.

PURPOSE: To investigate the prognostic value of serum transferrin (TRF) level before intensity-modulated radiation therapy (IMRT) on radio-sensitivity and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). METHODS: From October 2012 to October 2016, a total of 348 patients with NPC in the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed in our study. The concentration of serum TRF was detected by the method of enzyme-linked immunosorbent assay (ELISA). In the whole group, 46 patients received IMRT, and 302 patients received IMRT plus chemotherapy. The radio-sensitive tumor was defined when the local tumor lesions disappeared completely in the nasopharyngeal MRI scan and no tumor residues were found under the electronic nasopharyngoscope one month after the end of radiotherapy. RESULTS: The serum TRF level before IMRT was (1.34-3.89) g/L, with a median of 2.16 g/L and a mean of (2.20 ± 0.42) g/L. In the whole group, 242 cases (69.5%) were radiosensitive, and 106 cases (30.5%) were insensitive. The number of radiosensitive patients in the group of HTRF (transferrin > 2.16 g/L) and LTRF (transferrin ≤ 2.16 g/L) before radiotherapy was 129 (74.6%) and 113 (64.6%), respectively. The difference in radio-sensitivity between the two groups was statistically significant (χ2 = 4.103, p = 0.043). Logistic regression analysis showed that the level of TRF before radiotherapy (OR = 1.702; 95% CI 1.044~2.775; p = 0.033) was an independent factor for radio-sensitivity. The log-rank test showed that patients in the LTRF group achieved a significantly worse OS (χ2 = 5.388, p = 0.02) than those in the HTRF group. Cox regression analysis showed that baseline TRF level (HR = 1.706; 95% CI 1.065~2.731; p = 0.026) was an independent prognostic factor for overall survival. CONCLUSIONS: The low level of TRF before IMRT is a risk factor for radio-sensitivity and a prognostic factor for poor OS in NPC patients. It may be a promising marker to predict radio-sensitivity and OS in NPC patients who accept IMRT.

Boosting activity on copper functionalized biomass graphene by coupling nanocrystalline Nb2O5 as impressive rate capability for supercapacitor and outstanding catalytic activity for oxygen reduction.

A novel and hierarchical porous but cross-linked copper-doped biomass graphene (Cu@HPBG) combined with Nb2O5 (denoted as Nb2O5/Cu@HPBG) is successfully fabricated on a large-scale using fig peels as biomass carbon and copper as the graphitization catalyst. During the synthesis process, basic copper carbonate serves dual functions of pore-forming agent, as well as homogeneous copper provider, and NH3 is employed as a defect-forming agent and N dopant. Owing to the porous hierarchical structure increased availability of contact interface and pseudo capacitance active sites provided by copper and Nb2O5, the assembled asymmetrical supercapacitor (ASC) employing Nb2O5/Cu@HPBG as positive electrode and HPBG as negative electrode can not only widen the stability window range of 0～1.9 V, but also deliver a maximum gravimetric energy density of 82.8 W h kg-1 at the power density of 950.0 W kg-1 and maintain a remarkable cycling stability of 97.1% after 15,000 cycles. Impressively, due to the synergistic enhancement of Cu@HPBG and Nb2O5, the resulting Nb2O5/Cu@HPBG hybrid displays more positive half wave potential (∼0.85 V) and a long-life stability than Pt/C electrode toward oxygen reduction reaction (ORR). Our research provides a feasible strategy to fabricate renewable biomass graphene electroactive composites for large-scale supercapacitor electrodes and efficient ORR catalysts toward energy applications.