DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment

Melanoma has been a serious threat to the human health; however, effective therapeutic methods of this cancer are still limited. Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy. In this paper, a chemo-immunotherapy system of DOX, IL-2 and IFN-γ based on poly(γ-ethyl-L-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-L-glutamate) (PELG-PEG-PELG) hydrogel was developed for local treatment of melanoma xenograft. The drug release process of this system exhibited a short term of burst release (the first 3 days), followed by a long-term sustained release (the following 26 days). The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats, showing a good biodegradability and biocompatibility. The DOX/IL-2/IFN-γ co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro, through increasing the ratio of cell apoptosis and G2/S phage cycle arrest. Moreover, the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model, which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Overall, the strategy of localized co-delivery of DOX/IL-2/IFN-γ using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy

Start-up scheme for converter station of MMC-HVDC based on single-clamp sub-module using in grid black start

Single-clamp sub-module (SCSM) combining the cost and technological advantages has become one of the next modular multilevel converter (MMC) sub-module topologies in response to DC fault aspect. It describes the topological structure and working conditions based on SCMMC (Single-Clamp MMC) and proposes the three-stage start-up processes of SCMMC. The paper has made a detailed study on the black-start scheme of the blackout terminal converter when SCMMC-HVDC is used in grid black start. The active-side SCMMC orderly rotation trigger control strategy and the passive-side SCMMC orderly rotation bypass control strategy are proposed targeted. The paper proposes the corresponding start-up procedures for the SCMMC-HVDC system. At last, simulation models are established in PSCAD/EMTDC, the simulation results have validated the efficiency of the proposed black-start scheme for the converter of the blackout terminal

Calculation method for equivalent model of AC filters in HVDC transmission system

AC filter is an important part of HVDC system, which can restrain the AC-side harmonics effectively and compensate for the reactive power consumed by converter station. Due to the harmonic characters of converter, double-tuned filter and triple-tuned filter are widely used in HVDC system. There is no model of double-tuned filter or triple-tuned filter in the common simulation software such as ETAP and DIgSILENT, which brought some difficulties to the simulation of HVDC especially harmonic analysis. To solve this problem, the accurate and simplified calculation method for equivalent models which instead double-tuned filter and triple-tuned filter by two parallel single-tuned filters or three parallel single-tuned filters are proposed. Furthermore, the accurate formulas and simplified formulas are given which can convert the parameters of double-tuned filter or triple-tuned filter to the parameters of parallel single-tuned filters. Taking into account of the complexity of the accurate formulas, the resonant frequencies of double-tuned filter and triple-tuned filter are considered in the simplified formulas, which simplified the computational complexity. Finally, the feasibility of the equating method and the validity of parameters calculation method are verified

pH-Responsive Poly(ethylene glycol)/Poly(l‑lactide) Supramolecular Micelles Based on Host–Guest Interaction

pH-responsive supramolecular amphiphilic micelles based on benzimidazole-terminated poly­(ethylene glycol) (PEG-BM) and β-cyclodextrin-modified poly­(l-lactide) (CD-PLLA) were developed by exploiting the host–guest interaction between benzimidazole (BM) and β-cyclodextrin (β-CD). The dissociation of the supramolecular micelles was triggered in acidic environments. An antineoplastic drug, doxorubicin (DOX), was loaded into the supramolecular micelles as a model drug. The release of DOX from the supramolecular micelles was clearly accelerated as the pH was reduced from 7.4 to 5.5. The DOX-loaded PEG-BM/CD-PLLA supramolecular micelles displayed an enhanced intracellular drug-release rate in HepG2 cells compared to the pH-insensitive DOX-loaded PEG-<i>b</i>-PLLA counterpart. After intravenous injection into nude mice bearing HepG2 xenografts by the tail vein, the DOX-loaded supramolecular micelles exhibited significantly higher tumor inhibition efficacy and reduced systemic toxicity compared to free DOX. Furthermore, the DOX-loaded supramolecular micelles showed a blood clearance rate markedly lower than that of free DOX and comparable to that of the DOX-loaded PEG-<i>b</i>-PLLA micelles after intravenous injection into rats. Therefore, the pH-responsive PEG-BM/CD-PLLA supramolecular micelles hold potential as a smart nanocarrier for anticancer drug delivery