Skeletal muscle disorders have posed great threats to health. Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging. Aptamers can improve targeting efficacy. In this study, for the first time, the human skeletal muscle-specific ssDNA aptamers (HSM01, etc.) were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro. The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells. Furthermore, the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo, suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes. Therefore, this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.
Background Previous studies have proven that ultraviolet (UV)-based phototherapy, including UVB or psoralen UVA (PUVA), and their combination therapies, is effective for psoriasis treatment. Objective To compare the clinical efficacy and adverse events (AEs) of different UV-based phototherapy in psoriasis. Methods PubMed, Cochrane Library, Scopus and Embase were systematically searched. A random-effect model network meta-analysis with frequentist framework was performed, and results were reported as risk ratios (RRs) with 95% CI. The main variable for assessing effectiveness and safety are PASI 75 response and withdrawal due to AEs. Ranking effects were calculated by surface under the cumulative ranking analysis (SUCRA). Results Thirty-two studies involving a total of 2120 psoriasis patients were included in this network meta-analysis. Overall, no significant difference was reported with respect to withdrawal due to AEs or incidence of erythema. The relatively safest strategy was combined adjuvant therapy with PUVA (cPUVA), especially PUVA combined with calcium/vitamin D derivatives (RR 0.98, 95% CI [0.30–3.17], SUCRA = 80.8%). Both cPUVA (RR 1.39, 95% CI [1.00– 1.94]) and combined adjuvant therapy with UVB (cUVB) (RR 1.27, 95% CI [1.03–1.57]) showed a superior effect than the monotherapy of UVA or UVB, respectively. PUVA combined with vitamin D and its derivatives (PAVD) ranked highest concerning clinical effect and safety (clusterank value = 7393.2). Conclusions The efficacy of all the combination therapy regimens was significantly superior to that of UV monotherapy, without significant differences in tolerability and safety. cUVB and cPUVA, and particularly the combination of UVA with calcium/vitamin D derivatives, was ranked as the overall safest and most effective phototherapy method.
To reduce the crosswind effect on high-speed trains, in this paper, by using the Improved Delayed Detached Eddy Simulation (IDDES) method and the SST (Formula presented.) turbulence model, a novel blowing measure is studied and compared by considering different positions of blowing slots on the train surface. The concerned blowing positions on the train surface include the top position (Top); windward side (WWS): the upper position (WU), middle position (WM), and lower position (WL); and leeward side (LWS): the upper position (LU), middle position (LM), and lower position (LL). The results show that in regard to the rolling moment coefficient around the leeward rail, CMxlee, the mitigation effect with LM for the head car is the largest, and the mitigation effect with WL for the middle car and tail car is superior to other cases. The corresponding drop percentages are 18.5%, 21.7%, and 30.8% for the head car, middle car, and tail car, respectively. The flow structures indicate that the blowing positions on the lower half of WWS and upper half of LWS would form a protective air gap to weaken the impact of coming flows and delay the vortex separation on LWS, and thus the train aerodynamic performance is improved. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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