RESUMO
Global sensitivity analysis combined with quantitative high-throughput screening (GSA-qHTS) uses random starting points of the trajectories in mixture design, which may lead to potential contingency and a lack of representativeness. Moreover, a scenario in which all factor levels were at stimulatory effects was not considered, thereby hindering a comprehensive understanding of GSA-qHTS. Accordingly, this study innovatively introduced an optimised experimental design, uniform design (UD), to generate non-random and representative sample points with smaller uniformity deviation as starting points of multiple trajectories. By combining UD with the previously optimised one-factor-at-a-time (OAT) method, a novel mixture design method was developed (UD-OAT). The single toxicity tests showed that three pyridinium and five imidazolium ionic liquids (ILs) exerted stimulatory effects on Vibrio qinghaiensis sp.-Q67; thus, four stimulatory effective concentrations of each IL were selected as factor levels. The UD-OAT generated 108 mixture samples with equal frequency and without repetition. High-throughput microplate toxicity analysis revealed that all 108 mixtures exhibited inhibitory effects. Among these, type B mixtures exhibited increasing toxicities that subsequently decreased, unlike type C mixtures, which consistently increased over time. GSA successfully identified three of the eight ILs as important factors influencing the toxicities of the mixtures. When individual ILs produced stimulatory effects, mixtures containing two to three ILs exhibited either stimulatory effects or none. In contrast, mixtures containing five to eight ILs exhibited inhibitory effects, while those containing four ILs showed a transition from stimulatory to inhibitory effects. This study provides a novel mixture design method for studying mixture toxicity and fills the application gap of GSA-qHTS. The phenomenon of individuals being beneficial while mixtures can be harmful challenges traditional mixture risk assessments.
RESUMO
BACKGROUND: This study aimed to observe clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel, medical collagen sponge and rhGM-CSF gel in combination with medical collagen sponge on deep second-degree burns of head, face or neck in infants. METHODS: A total of 108 infants with deep second-degree burns on head, face or neck were randomly divided into rhGM-CSF group, medical collagen sponge group, and rhGM-CSFâ +â medical collagen sponge group. The scab dissolving time, healing time, bacterial positive rate and Vancouver scar scale were evaluated and analyzed. RESULTS: The data analysis showed that scab dissolving time and healing time were shorter in rhGM-CSFâ +â medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group, and the difference was statistically significant (Pâ <â .05). Bacterial positive rate was lower in rhGM-CSFâ +â medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (Pâ <â .05). After 3 months, score of Vancouver scar scale (scar thickness, pliability, pigmentation and vascularity) was less in rhGM-CSFâ +â medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (Pâ <â .05). CONCLUSION: rhGM-CSF gel in combination with medical collagen sponge is significantly effective in treating deep second-degree burns of head, face or neck in infants. This combination is beneficial for infection control, acceleration of scab dissolving and wound healing, and reduction of scar hyperplasia and pigmentation, which is worthy of clinical application and promotion.
Assuntos
Queimaduras , Cicatriz , Lactente , Humanos , Colágeno/uso terapêutico , Resultado do Tratamento , Queimaduras/tratamento farmacológicoRESUMO
Semaphorin 3A (Sema3A) has recently been proven to play an essential role in tumorigenesis. Here, the role of Sema3A in ovarian cancer is explored. The prognostic value of Sema3A was evaluated using the Kaplan-Meier plotter database, and stable expression cells were established by the delivery of lentivirus harboring SEMA3A cDNA or shRNA into OVCA433 and SKOV3 cells, respectively. Then CCK-8 assay, colony-formation assay, wound-healing assay, and Transwell assay were utilized to verify the effect of Sema3A on tumorigenesis. Co-cultures of ovarian cancer cells (OVCA433 and SKOV3) with a conditional medium collected from the established cells were further utilized to confirm the function of Sema3A. Then, the RNA-seq assay was adopted to explore the underlying mechanism. The results demonstrated that low expression of Sema3A was predictive of poor overall survival in patients with ovarian cancer. Functional experiments revealed that Sema3A inhibited proliferation, migration, and invasion in ovarian cancer cells. Secreted Sema3A in a conditioned culture medium also exhibited an anti-tumor effect in ovarian cancer cells. RNA-seq assay suggested that focal adhesion and Lin28B were involved in regulating Sema3A. Rescue assays further verified that Lin28B/ROCK1 axis was vital in the regulation of Sema3A and Lin28B significantly upregulated ROCK1 through let-7g microRNA. The presented data indicate that Sema3A inhibits proliferation and metastasis via the downregulation of Lin28B/ROCK1 in ovarian cancer.
Assuntos
Neoplasias Ovarianas , Proteínas de Ligação a RNA , Semaforina-3A , Feminino , Humanos , Carcinogênese , Proliferação de Células , Regulação para Baixo , MicroRNAs/genética , Neoplasias Ovarianas/genética , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Semaforina-3A/genética , Semaforina-3A/metabolismoRESUMO
All-solid-state bulk-type lithium ion batteries (LIBs) are considered ultimate solutions to the safety issues associated with conventional LIBs using flammable liquid electrolyte. The development of bulk-type all-solid-state LIBs has been hindered by the low loading of active cathode materials, hence low specific surface capacity, and by the high interface resistance, which results in low rate and cyclic performance. In this contribution, we propose and demonstrate a synergistic all-composite approach to fabricating flexible all-solid-state LIBs. PEO-based composite cathode layers (filled with LiFePO4 particles) of â¼300 µm in thickness and composite electrolyte layers (filled with Al-LLZTO particles) are stacked layer-by-layer with lithium foils as negative layer and hot-pressed into a monolithic all-solid-state LIB. The flexible LIB delivers a high specific discharge capacity of 155 mAh/g, which corresponds to an ultrahigh surface capacity of 10.8 mAh/cm2, exhibits excellent capacity retention up to at least 10 cycles and could work properly under harsh operating conditions such as bending or being sectioned into pieces. The all-composite approach is favorable for improving both mesoscopic and microscopic interfaces inside the all-solid-state LIB and may provide a new toolbox for design and fabrication of all-solid-state LIBs.